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European Ancestry (european + ancestry)
Selected AbstractsSequence Variations of the Human MPDZ Gene and Association With Alcoholism in Subjects With European AncestryALCOHOLISM, Issue 4 2009Victor M. Karpyak Background:,Mpdz gene variations are known contributors of acute alcohol withdrawal severity and seizures in mice. Methods:, To investigate the relevance of these findings for human alcoholism, we resequenced 46 exons, exon,intron boundaries, and 2 kilobases in the 5, region of the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a history of alcohol withdrawal without AWS, and 64 Coriell samples from self-reported nonalcoholic subjects [all European American (EA) ancestry] and compared with the Mpdz sequences of 3 mouse strains with different propensity to AWS. To explore potential associations of the human MPDZ gene with alcoholism and AWS, single SNP and haplotype analyses were performed using 13 common variants. Results:, Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequence comparison revealed that the human gene does not have variations identical to those comprising Mpdz gene haplotype associated with AWS in mice. We also found no significant association between MPDZ haplotypes and AWS in humans. However, a global test of haplotype association revealed a significant difference in haplotype frequencies between alcohol-dependent subjects without AWS and Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism and/or related phenotypes other than AWS. Haplotype-specific tests for the most common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found to be significantly more prevalent in alcoholics without AWS compared with nonalcoholic Coriell subjects (p = 0.019). Conclusions:, Sequencing of MPDZ gene in individuals with EA ancestry revealed no variations in the sites identical to those associated with AWS in mice. Exploratory haplotype and single SNP association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not AWS. Further functional genomic analysis of MPDZ variants and investigation of their association with a broader array of alcoholism-related phenotypes could reveal additional genetic markers of alcoholism. [source] Effect of pioglitazone on insulin sensitivity, vascular function and cardiovascular inflammatory markers in insulin-resistant non-diabetic Asian IndiansDIABETIC MEDICINE, Issue 5 2006A. Raji Abstract Aims To determine the effects of pioglitazone (30 mg once daily for 16 weeks) on insulin sensitivity, insulin-mediated vasodilation, vascular inflammatory markers, fat distribution and lipids in Asian Indians and Caucasians of European ancestry. Methods Cross-sectional study. Eighteen non-diabetic Asian Indians and 17 Caucasians of comparable age (34 ± 3 vs. 36 ± 3 years) and body mass index (26.0 ± 1.2 vs. 24.7 ± 1.0 kg/m2) had measurements of insulin sensitivity (M, insulin clamp at 6 pmol/kg per min), abdominal fat (computed tomographic scan at L4-L5), endothelial-dependent (reactive hyperaemia, RH) and -independent (0.4 mg sublingual nitroglycerin, TNG) vasodilation using brachial artery ultrasound before and after the 2-h clamp at baseline and after pioglitazone therapy. Results Asian Indians were insulin resistant compared with Causasians during the baseline clamp (M = 25.6 ± 1.7 vs. 41.1 ± 2.2 µmol/kg per min, P < 0.0001) and improved significantly after pioglitazone (to 33.9 ± 1.7 µmol/kg per min, P < 0.001). Vasodilatory responses to RH and TNG were similar in Asian Indians and Caucasians at baseline and did not change. Insulin-mediated vasodilation improved after pioglitazone in Asian Indians, but not in Caucasians, and correlated with the change in insulin sensitivity (r = 0.52, P = 0.03). C-reactive protein (CRP) was higher in Asian Indians vs. Caucasians (1.6 ± 0.4 vs. 0.9 ± 0.2 mg/l) and was negatively correlated with insulin sensitivity (r = ,0.53, P = 0.02). In the Asian Indian group, CRP and plasminogen activator inhibitor-1 decreased and adiponectin increased after pioglitazone, but there were no significant changes in total or visceral fat. Conclusions These results demonstrate that insulin-resistant Asian Indians respond favourably to an insulin sensitizer with improvements in insulin sensitivity, cardiovascular and inflammatory risk markers, and vascular responses to insulin. These agents may have a role in decreasing the risk of diabetes and cardiovascular disease in this high-risk population. [source] Polymorphisms in the thymidylate synthase promoter and the DNA repair genes XRCC1 and XPD in a Brazilian populationENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2006Renata Canalle Abstract Polymorphisms in genes responsible for maintaining genomic integrity are potential modifiers of disease risk. Since considerable interindividual and interethnic variation in DNA repair capacity has been associated with polymorphic alleles, we evaluated the frequency of the 2R/3R variants in the TS promoter, Arg194Trp and Arg399Gln in the XRCC1 gene, and Asp312Asn and Lys751Gln in the XPD gene in 364 healthy individuals from a Brazilian population separated by ethnicity (European ancestry and African ancestry). The genotypes were determined by PCR (TS) or by PCR-RFLP (XRCC1 and XPD). The frequency of the TS 3R allele was 0.56 for whites and 0.51 for nonwhites. In the case of the XRCC1 MspI polymorphism, the allele frequencies were 0.09 for 194Trp in both nonwhites and whites and 0.27 and 0.28 for 399Gln in nonwhites and whites, respectively. For the XPD 312Asn allele, we found a frequency of 0.25 in white individuals, which was significantly different (P = 0.025) from that seen in nonwhites (0.15). Similarly, the 751Gln polymorphic allele of the XPD gene was significantly more frequent (P < 0.002) in whites (0.30) than in nonwhites (0.20). The genotype frequencies were within Hardy,Weinberg equilibrium. We concluded that the genotype and allele frequencies of XPD gene polymorphism differed between white and nonwhite Brazilians, and that the frequencies of the XPD 312Asn and XRCC1 399Gln alleles in this Brazilian population showed ethnic variability when compared with those observed in other populations. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source] TEMPORAL PATTERN OF AFRICANIZATION IN A FERAL HONEYBEE POPULATION FROM TEXAS INFERRED FROM MITOCHONDRIAL DNAEVOLUTION, Issue 5 2004M. Alice Pinto Abstract The invasion of Africanized honeybees (Apis mellifera L.) in the Americas provides a window of opportunity to study the dynamics of secondary contact of subspecies of bees that evolved in allopatry in ecologically distinctive habitats of the Old World. We report here the results of an 11-year mitochondrial DNA survey of a feral honeybee population from southern United States (Texas). The mitochondrial haplotype (mitotype) frequencies changed radically during the 11-year study period. Prior to immigration of Africanized honeybees, the resident population was essentially of eastern and western European maternal ancestry. Three years after detection of the first Africanized swarm there was a mitotype turnover in the population from predominantly eastern European to predominantly A. m. scutellata (ancestor of Africanized honeybees). This remarkable change in the mitotype composition coincided with arrival of the parasitic mite Varroa destructor, which was likely responsible for severe losses experienced by colonies of European ancestry. From 1997 onward the population stabilized with most colonies of A. m. scutellata maternal origin. [source] MHC microsatellites in a Southern Brazilian populationINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2009C. Sens-Abuázar Summary Microsatellites are short tandem repeats of 1,6 bp DNA fragments, which are found throughout the genome. Due to their high levels of polymorphism, many of them are used as markers for population studies. Here we report an investigation on four microsatellites (D6S273, D6S2792, STR_MICA and D6S2810) located within the major histocompatibility complex in a sample of 281 Southern Brazilians of European ancestry. Allelic and haplotypic frequencies are described, as well as linkage disequilibrium (LD) between alleles of these microsatellites and alleles of three HLA genes: HLA-B, HLA-DRB1 and HLA-DQB1. The most polymorphic microsatellite was D6S2810, located close to the HLA-B locus. Strong LD was observed between alleles of microsatellites and HLA genes. The strongest associations occurred among STR_MICA*A5.1,HLA-B*13, STR_MICA*A6,HLA-B*49, STR_MICA*A9,HLA-B*39, STR_MICA*A9,HLAB*57, D6S2810*334,HLA-B*14, D6S2810*334,HLA-B*38, STR_MICA*A5.1,HLA-DRB1*1501,HLA-DQB1*0602 and D6S2810*344,HLA-DRB1*0411,HLA-DQB1*0302. This study contributes with important information on HLA haplotypes, and is potentially useful in resolving cases of low resolution HLA genotyping ambiguities. [source] Association with replication between estrogen-related receptor , (ESRR,) Polymorphisms and bone phenotypes in women of European ancestryJOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2010Latifa Elfassihi Abstract Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor , (ESRR,) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRR, sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20,kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRR, in the determination of bone density in women. © 2010 American Society for Bone and Mineral Research [source] Effects of Variation at the ALDH2 Locus on Alcohol Metabolism, Sensitivity, Consumption, and Dependence in EuropeansALCOHOLISM, Issue 7 2006Peter A. Dickson Background: The low-activity variant of the aldehyde dehydrogenase 2 (ALDH2) gene found in East Asian populations leads to the alcohol flush reaction and reduces alcohol consumption and risk of alcohol dependence (AD). We have tested whether other polymorphisms in the ALDH2 gene have similar effects in people of European ancestry. Methods: Serial measurements of blood and breath alcohol, subjective intoxication, body sway, skin temperature, blood pressure, and pulse were obtained in 412 twins who took part in an alcohol challenge study. Participants provided data on alcohol reactions, alcohol consumption, and symptoms related to AD at the time of the study and subsequently. Haplotypes based on 5 single-nucleotide polymorphisms (SNPs) were used in tests of the effects of variation in the ALDH2 gene on alcohol metabolism and alcohol's effects. Results: The typed SNPs were in strong linkage disequilibrium and 2 complementary haplotypes comprised 83% of those observed. Significant effects of ALDH2 haplotype were observed for breath alcohol concentration, with similar but smaller and nonsignificant effects on blood alcohol. Haplotype-related variation in responses to alcohol, and reported alcohol consumption, was small and not consistently in the direction predicted by the effects on alcohol concentrations. Conclusions: Genetic variation in ALDH2 affects alcohol metabolism in Europeans. However, the data do not support the hypothesis that this leads to effects on alcohol sensitivity, consumption, or risk of dependence. [source] Common genetic variants associated with plasma fibrin D-dimer concentration in older European- and African-American adultsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2008L. A. LANGE Summary.,Background and Objectives:,D-dimer is a hemostasis marker that reflects ongoing fibrin formation and degradation. There is significant inter-individual and inter-population variability in D-dimer concentration, but whether genetic factors underlie these differences is largely unknown. We hypothesized that common coagulation gene variants contribute to differences in circulating D-dimer concentration. Methods:,The setting was European-American (EA; n = 1858) and African-American (AA; n = 327) unrelated older adults from the Cardiovascular Health Study (CHS), in which we genotyped SNPs in 42 genes related to blood coagulation and fibrinolysis. Results:,Several fibrinogen gene polymorphisms, including the Thr312Ala A, chain variant and the FGG-10034 C/T variant, were associated with ,20% higher plasma D-dimer levels in EA (false discovery rate < 5% for covariate-adjusted model). There was also some evidence that a Pro41Leu variant of the PLAU gene encoding urinary plasminogen activator and non-coding polymorphism of the plasminogen activator inhibitor type 1 gene (SERPINE1) were associated with higher plasma D-dimer in EA. There were no significant associations between the studied coagulation or fibrinolysis gene SNPs and plasma D-dimer levels in the smaller AA sample. However, each standard deviation increase in European ancestry assessed by ancestry-informative gene markers was associated with ,10% lower mean D-dimer levels in AA. Conclusions:,Together, common coagulation/fibrinolysis gene SNPs explained only ,2% of the variance in plasma D-dimer levels in EA. These findings suggest that the association of D-dimer with risk of vascular outcomes may be mediated largely by environmental factors, other genes, and/or genetic interactions. [source] Review article: the modern diagnosis and management of haemochromatosisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2006P. C. ADAMS Summary Haemochromatosis is the most common genetic disease in populations of European ancestry. Despite estimates based on genetic testing in Caucasian populations of 1 in 227, many physicians consider haemochromatosis to be a rare disease. The diagnosis can be elusive because of the non-specific nature of the symptoms. Of all the symptoms, liver disease has the most consistent relationship to haemochromatosis and the prognosis of haemochromatosis is most closely linked to the degree of iron overload. With the discovery of the HFE gene in 1996, comes new insights into the pathogenesis of the disease and new diagnostic strategies. However, a growing number of new iron-related genes have been discovered and linked to other iron overload syndromes. [source] Origin of honeybees (Apis mellifera L.) from the Yucatan peninsula inferred from mitochondrial DNA analysisMOLECULAR ECOLOGY, Issue 6 2001Kylea E. Clarke Abstract Honeybees (Apis mellifera L.) sampled at sites in Europe, Africa and South Ámerica were analysed using a mitochondrial DNA restriction fragment length polymorphism (RFLP) marker. These samples were used to provide baseline information for a detailed analysis of the process of Africanization of bees from the neotropical Yucatan peninsula of Mexico. Radical changes in mitochondrial haplotype (mitotype) frequencies were found to have occurred in the 13-year period studied. Prior to the arrival of Africanized bees (1986) the original inhabitants of the Yucatan peninsula appear to have been essentially of southeastern European origin with a smaller proportion having northwestern European ancestry. Three years after the migration of Africanized bees into the area (1989), only very low levels of maternal gene flow from Africanized populations into the resident European populations had occurred. By 1998, however, there was a sizeable increase in the proportion of African mitotypes in domestic populations (61%) with feral populations having 87% of mitotypes classified as African derived. The results suggest that the early stages of Africanization did not involve a rapid replacement of European with African mitotypes and that earlier studies probably overestimated the prevalence of African mitotypes. [source] Genetic composition of Brazilian population samples based on a set of twenty-eight ancestry informative SNPsAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 2 2010Tulio C. Lins Ancestry informative SNPs can be useful to estimate individual and population biogeographical ancestry. Brazilian population is characterized by a genetic background of three parental populations (European, African, and Brazilian Native Amerindians) with a wide degree and diverse patterns of admixture. In this work we analyzed the information content of 28 ancestry-informative SNPs into multiplexed panels using three parental population sources (African, Amerindian, and European) to infer the genetic admixture in an urban sample of the five Brazilian geopolitical regions. The SNPs assigned apart the parental populations from each other and thus can be applied for ancestry estimation in a three hybrid admixed population. Data was used to infer genetic ancestry in Brazilians with an admixture model. Pairwise estimates of Fst among the five Brazilian geopolitical regions suggested little genetic differentiation only between the South and the remaining regions. Estimates of ancestry results are consistent with the heterogeneous genetic profile of Brazilian population, with a major contribution of European ancestry (0.771) followed by African (0.143) and Amerindian contributions (0.085). The described multiplexed SNP panels can be useful tool for bioanthropological studies but it can be mainly valuable to control for spurious results in genetic association studies in admixed populations. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source] AKAP10 (I646V) functional polymorphism predicts heart rate and heart rate variability in apparently healthy, middle-aged European-AmericansPSYCHOPHYSIOLOGY, Issue 3 2009Serina A. Neumann Abstract Previous evidence suggests that the dual-specific A kinase-anchoring protein 2 functional polymorphism (AKAP10 (A/G) I646V) influences heart rate (HR) and heart rate variability (HRV) in mice and humans (N=122) with cardiovascular disease. Here, we asked whether this AKAP10 variant predicts HR and HRV in a large sample of healthy humans. Resting HR and short-term time and frequency domain measures of HRV (5 min during paced and unpaced respiration conditions) were assessed in a U.S. community sample (N=1,033) of generally healthy men and women (age 30,54) of European ancestry. Each person was genotyped for the AKAP10 variant. As with previous work, the AKAP10 Val allele predicted greater resting HR (Paced p<.01; Unpaced p<.03) and diminished HRV (Paced ps <.05) suggesting that this variant may modulate the sensitivity of cardiac pacemaker cells to autonomic inputs, possibly conferring risk for arrhythmias and sudden cardiac death. [source] Brief communication: Admixture analysis with forensic microsatellites in Minas Gerais, Brazil: The ongoing evolution of the capital and of an African-derived communityAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 4 2009Marília O. Scliar Abstract We report the estimated allele frequencies for 13 and 14 microsatellite loci in two populations of Minas Gerais, Brazil as follows: Belo Horizonte (the capital) and Marinhos (an African-derived community). Analysis of the African, Amerindian, and European genetic contributions to both populations, together with historical information, revealed distinct differences between the two populations. Estimates for Belo Horizonte revealed a higher-European (66%) than African (32%) contribution, and a minimal Amerindian contribution. These results are consistent with the peopling of the city mainly by people from the Minas Gerais hinterland, a people highly admixed but with more European ancestry. Estimates for Marinhos confirmed the high-African component of the population. However, a temporal analysis of two datasets,CURRENT (representing the population living in Marinhos today) and ORIGINAL (representing families, who have lived in Marinhos since the onset of the 20th century),,identified a diminishing of the population's African ancestry from 92% in the ORIGINAL group to 67% in the CURRENT group. This change is here interpreted as a consequence of the growing migration into the village of people with more European ancestry and subsequent admixture with the local population. Am J Phys Anthropol, 2009. © 2009 Wiley-Liss, Inc. [source] Parkinson's Disease and Low Frequency Alleles Found Together Throughout LRRK2ANNALS OF HUMAN GENETICS, Issue 4 2009Coro Paisán-Ruiz Summary Mutations within LRRK2, most notably p.G2019S, cause Parkinson's disease (PD) in rare monogenic families, and sporadic occurrences in diverse populations. We investigated variation throughout LRRK2 (84 SNPs; genotype or diplotype found for 49 LD blocks) for 275 cases (European ancestry, onset at age 60 or older) and 275 neurologically healthy control subjects (NINDS Neurogenetics Repository). Three grade-of-membership groups, i.e. genetic risk sets, were identified that exactly matched many subjects (cases: 46, 4, 137; controls: 0, 178, 0), and distinguished 94% of the subjects (i.e. >50% likeness to one set). Set I, affected, carried certain low frequency alleles located in multiple functional domains. Set II was unaffected. Set III, also affected, resembled set II except for slightly elevated frequencies of minor alleles not defining set I. We conclude that certain low frequency alleles distributed throughout LRRK2 are a genetic background to a third of cases, defining a distinct subset. [source] Three Common Intronic Variants in the Maternal and Fetal Thiamine Pyrophosphokinase Gene (TPK1) are Associated with Birth WeightANNALS OF HUMAN GENETICS, Issue 5 2007D. Fradin Summary Extreme variations in birth weight increase immediate postnatal mortality and morbidity, and are also associated with the predisposition to metabolic diseases in late adulthood. Birth weight in humans is influenced by yet unknown genetic factors. Since the 7q34-q35 region showed linkage with birth weight in a recent human genome scan (p = 8.10,5), this study investigated the TPK1 (thiamine pyrophosphokinase) gene locus, located in 7q34-36. Having found no coding variants in the TPK1 gene, we genotyped 43 non coding SNPs spanning a region of 420kb, and used the QTDT method to test their association with birth weight in 964 individuals from 220 families of European ancestry. Family-based tests detected association of 8 SNPs with birth weight (p<0.008), but after correction for multiple tests only rs228581 C/T (p = 0.03), rs228582 A/G (p = 0.04) and rs228584 C/T (p = 0.03) were still associated with birth weight, as well as their T-A-T haplotype (p = 0.03). In addition, we found an association between maternal rs228584 genotype and offspring birth weight (p = 0.027). These observations suggest that genomic variations in the fetal and maternal TPK1 gene could contribute to the variability of birth weight in normal humans. [source] The Causal Element for the Lactase Persistence/ non-persistence Polymorphism is Located in a 1 Mb Region of Linkage Disequilibrium in EuropeansANNALS OF HUMAN GENETICS, Issue 4 2003M. Poulter Summary Expression of lactase in the intestine persists into adult life in some people and not others, and this is due to a cis -acting regulatory polymorphism. Previous data indicated that a mutation leading to lactase persistence had occurred on the background of a 60 kb 11-site LCT haplotype known as A (Hollox et al. 2001). Recent studies reported a 100% correlation of lactase persistence with the presence of the T allele at a CT SNP at ,14 kb from LCT, in individuals of Finnish origin, suggesting that this SNP may be causal of the lactase persistence polymorphism, and also reported a very tight association with a second SNP (GA ,22 kb) (Enattah et al. 2002). Here we report the existence of a one megabase stretch of linkage disequilibrium in the region of LCT and show that the ,14 kb T allele and the ,22 kb A allele both occur on the background of a very extended A haplotype. In a series of Finnish individuals we found a strong correlation (40/41 people) with lactose digestion and the presence of the T allele. The T allele was present in all 36 lactase persistent individuals from the UK (phenotyped by enzyme assay) studied, 31/36 of whom were of Northern European ancestry, but not in 11 non-persistent individuals who were mainly of non-UK ancestry. However, the CT heterozygotes did not show intermediate lactase enzyme activity, unlike those previously phenotyped by determining allelic transcript expression. Furthermore the one lactase persistent homozygote identified by having equally high expression of A and B haplotype transcripts, was heterozygous for CT at the ,14 kb site. SNP analysis across the 1 megabase region in this person showed no evidence of recombination on either chromosome between the ,14 kb SNP and LCT. The combined data shows that although the ,14 kb CT SNP is an excellent candidate for the cause of the lactase persistence polymorphism, linkage disequilibrium extends far beyond the region searched so far. In addition, the CT SNP does not, on its own, explain all the variation in expression of LCT, suggesting the possibility of genetic heterogeneity. [source] The FAS ,670A>G polymorphism influences susceptibility to systemic sclerosis phenotypesARTHRITIS & RHEUMATISM, Issue 12 2009J. Broen Objective To investigate the possible role of the FAS ,670A>G functional polymorphism in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. Methods A total of 2,900 SSc patients and 3,186 healthy controls were included in this study. We analyzed the genotype and allele frequencies of the FAS ,670A>G polymorphism in 9 distinct ethnic cohorts, including 6 cohorts of European ancestry (a Spanish cohort of 228 SSc patients and 265 controls, a Dutch cohort of 203 SSc patients and 277 controls, a German cohort of 313 SSc patients and 247 controls, an Italian cohort of 323 SSc cases and 89 controls, a British cohort of 269 SSc patients, and a Swedish cohort of 182 patients) and 3 distinct ethnic cohorts from the US (a cohort of 1,047 white patients and 692 controls, a cohort of 159 Hispanic patients and 137 controls, and a cohort of 176 black SSc patients and 194 controls). Genotyping was performed using a TaqMan 5, allelic discrimination assay. Results In the British, Italian, and American white cohorts we observed an association of the FAS ,670G allele with limited cutaneous SSc (lcSSc) (odds ratios [ORs] 1.25, 1.43, and 1.18, respectively). A meta-analysis comprising all 9 cohorts revealed an association of both the FAS ,670G allele (OR 1.10) and the FAS ,670GG genotype (OR 1.13) with the lcSSc phenotype. In a meta-analysis including only white subjects, both the FAS ,670G allele and the FAS ,670GG genotype remained associated with lcSSc (allele OR 1.12; genotype OR 1.16). In addition, a recessive model of the ,670GG genotype exhibited a strong association with SSc, lcSSc, and anticentromere antibody,positive lcSSc (OR 1.23, OR 1.33, and OR 1.45, respectively). Conclusion Our data show that the FAS ,670A>G polymorphism plays a role in lcSSc susceptibility. A similar trend has been observed in other autoimmune diseases. [source] European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 8 2009Sharon A. Chung Objective To determine whether genetic substructure in European-derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease. Methods SLE patients of European descent (n = 1,754) from 8 case collections were genotyped for >1,400 ancestry informative markers that define a north,south gradient of European substructure. Using the Structure program, each SLE patient was characterized in terms of percent Northern (versus percent Southern) European ancestry based on these genetic markers. Nonparametric methods, including tests for trend, were used to identify associations between Northern European ancestry and specific SLE manifestations. Results In multivariate analyses, increasing levels of Northern European ancestry were significantly associated with photosensitivity (Ptrend = 0.0021, odds ratio for highest quartile of Northern European ancestry versus lowest quartile [ORhigh,low] 1.64, 95% confidence interval [95% CI] 1.13,2.35) and discoid rash (Ptrend = 0.014, ORhigh,low 1.93, 95% CI 0.98,3.83). In contrast, increasing levels of Northern European ancestry had a protective effect against the production of anticardiolipin autoantibodies (Ptrend = 1.6 × 10,4, ORhigh,low 0.46, 95% CI 0.30,0.69) and anti,double-stranded DNA autoantibodies (Ptrend = 0.017, ORhigh,low 0.67, 95% CI 0.46,0.96). Conclusion This study demonstrates that specific SLE manifestations vary according to Northern versus Southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure based on genetic ancestry. [source] The PRL ,1149 G/T polymorphism and rheumatoid arthritis susceptibilityARTHRITIS & RHEUMATISM, Issue 5 2009Yvonne C. Lee Objective Previous studies have demonstrated that the PRL ,1149 T (minor) allele decreases prolactin expression and may be associated with autoimmune disease. The aim of this study was to determine the role of the PRL ,1149 G/T polymorphism (rs1341239) in rheumatoid arthritis (RA) susceptibility. Methods We examined the association between PRL ,1149 G/T and RA risk in 4 separate study populations, consisting of a total of 3,405 RA cases and 4,111 controls of self-reported white European ancestry. Samples were genotyped using 1 of 3 genotyping platforms, and strict quality control metrics were applied. We tested for association using a 2-tailed Cochran-Mantel-Haenszel additive, fixed-effects model. Results In the individual populations, odds ratios (ORs) for an association between PRL ,1149 T and RA risk ranged from 0.80 to 0.97. In a joint meta-analysis across all 4 populations, the OR for an association between PRL ,1149 T and RA risk was 0.90 (95% confidence interval 0.84,0.96, P = 0.001). Conclusion Our findings indicate a possible association between the PRL ,1149 T allele and decreased RA risk. The effect size is small but similar to ORs for other genetic polymorphisms associated with complex traits, including RA. [source] Risk factors for breast cancer in East Asian women relative to women in the WestASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 4 2009Christine S PERRY Abstract The incidence of breast cancer in women of East Asian ancestry (Chinese, Japanese and Korean) is lower than in women of European ancestry but is currently rising. This review explores potential reasons for this inter-ethnic difference in incidence by profiling breast cancer risk factors reported for East Asian and Western women. Factors such as endogenous hormone exposure, lifestyle choices, diet and genetic predisposition are associated with breast cancer risk in both East Asian and Western women. However, the relative exposure to these risk factors may vary according to a woman's geographical ancestry and culture. For example, age at menarche and menopause, parity, breast-feeding history, low fat and high soy consumption as well as the prevalence of high risk genetic alleles may vary with a woman's geographical ancestry and/or culture. Differences in exposure to these risk factors in East Asian and Western women are consistent with the inter-ethnic differences in breast cancer incidence observed. Understanding the underlying factors contributing to differences in the profile of breast cancer across populations is important when considering screening and prevention programs for East Asian women resident in the East or the West. [source] | |||||||||||||