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Genotype Combinations (genotype + combination)

Distribution by Scientific Domains

Medical Sciences	61%
Life Sciences	15%

Selected Abstracts

S19.3: Genotype combinations of plasminogen activator inhibitor-1 and angiotensin converting enzyme genes and risk for early onset of coronary heart disease

BIOMETRICAL JOURNAL, Issue S1 2004
Michael Löw
No abstract is available for this article. [source]

ACE and angiotensinogen gene genotypes and left ventricular mass in athletes

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2001
F. Diet
Background Genetic factors may be important in modifying heart size due to long-term athletic training. The significance of polymorphisms of genes of the renin,angiotensin system in myocardial mass in a population of athletes participating in different disciplines is not known. Methods The angiotensin I-converting enzyme gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and angiotensin II type 1 receptor gene A1166C polymorphism were determined in 83 male Caucasian endurance athletes and associated with left ventricular mass. Results No association with left ventricular mass was found for the polymorphisms of angiotensin I-converting enzyme gene I/D, angiotensinogen gene M235T and angiotensin II type 1 gene A1166C when studied separately. However, combined analysis of the angiotensin I-converting enzyme gene I/D polymorphism and angiotensinogen gene M235T polymorphism genotypes suggested an association with left ventricular mass (g m,2) (P = 0·023). Athletes with the angiotensin I-converting enzyme gene DD/angiotensinogen gene TT genotype combination had greater left ventricular mass compared with all other genotype combinations (179·8 ± 26·1 g m,2 vs. 145·2 ± 27·3 g m,2, P = 0·003). Conclusions These results suggest an association of combined angiotensin I-converting enzyme gene I/D polymorphism genotypes, and angiotensinogen gene M235T polymorphism genotypes with left ventricular hypertrophy due to long-term athletic training. A synergistic effect of angiotensin I-converting enzyme gene DD genotype and angiotensinogen gene TT genotype on left ventricular mass in endurance athletes appears to occur. [source]

IL-18 gene promoter ,137C/G and ,607C/A polymorphisms in Chinese Han children with type 1 diabetes mellitus

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2007
G. P. Dong
Summary Type 1 diabetes mellitus (T1DM) is a heterogeneous autoimmune disease, and both environmental and genetic factors play a role in its pathogenesis. Interleukin (IL)-18 is a potent pro-inflammatory cytokine capable of inducing interferon-gamma production that is associated with the development of T1DM. The gene for IL-18 is located on chromosome 11q22.2-q22.3 and has been reported to be associated with a susceptibility to T1DM. To test the putative involvement between IL-18 gene polymorphism and predisposition to T1DM, we conducted a case-control study in Chinese Han children. The single nucleotide polymorphisms at position ,607(C/A) and ,137(C/G) in the promoter region of the IL-18 gene were analysed by sequence-specific primers-polymerase chain reaction in 118 patients with T1DM and 150 healthy controls. (1) The allele frequency of ,607A was 41.2% and 53.0%, respectively, in patients and in control subjects (P = 0.01), but the allele frequency of ,137C/G was not statistically significant (P = 0.37). (2) The distribution of CC genotype at position ,607 was significantly different between patients and normal controls (P = 0.03), while the distribution of AA genotype in patients was significantly lower than that in the controls (P = 0.03). (3) Furthermore, there was a significant increase in haplotype (,137C/,607G) and genotype combination (,137GG/ ,607CC) in patients compared with controls (P = 0.03 and P = 0.04, respectively). The results of this study show that IL-18 gene promoter polymorphisms confer susceptibility to T1DM in Chinese Han children. Moreover, subjects carrying AA genotype at position ,607 of the promoter of IL-18 gene may be a low risk of T1DM development. [source]

Least-Square Deconvolution: A Framework for Interpreting Short Tandem Repeat Mixtures,

JOURNAL OF FORENSIC SCIENCES, Issue 6 2006
Tsewei Wang Ph.D.
ABSTRACT: Interpreting mixture short tandem repeat DNA data is often a laborious process, involving trying different genotype combinations mixed at assumed DNA mass proportions, and assessing whether the resultant is supported well by the relative peak-height information of the mixture sample. If a clear pattern of major,minor alleles is apparent, it is feasible to identify the major alleles of each locus and form a composite genotype profile for the major contributor. When alleles are shared between the two contributors, and/or heterozygous peak imbalance is present, it becomes complex and difficult to deduce the profile of the minor contributor. The manual trial and error procedures performed by an analyst in the attempt to resolve mixture samples have been formalized in the least-square deconvolution (LSD) framework reported here for two-person mixtures, with the allele peak height (or area) information as its only input. LSD operates on the peak-data information of each locus separately, independent of all other loci, and finds the best-fit DNA mass proportions and calculates error residual for each possible genotype combination. The LSD mathematical result for all loci is then to be reviewed by a DNA analyst, who will apply a set of heuristic interpretation guidelines in an attempt to form a composite DNA profile for each of the two contributors. Both simulated and forensic peak-height data were used to support this approach. A set of heuristic guidelines is to be used in forming a composite profile for each of the mixture contributors in analyzing the mathematical results of LSD. The heuristic rules involve the checking of consistency of the best-fit mass proportion ratios for the top-ranked genotype combination case among all four- and three-allele loci, and involve assessing the degree of fit of the top-ranked case relative to the fit of the second-ranked case. A different set of guidelines is used in reviewing and analyzing the LSD mathematical results for two-allele loci. Resolution of two-allele loci is performed with less confidence than for four- and three-allele loci. This paper gives a detailed description of the theory of the LSD methodology, discusses its limitations, and the heuristic guidelines in analyzing the LSD mathematical results. A 13-loci sample case study is included. The use of the interpretation guidelines in forming composite profiles for each of the two contributors is illustrated. Application of LSD in this case produced correct resolutions at all loci. Information on obtaining access to the LSD software is also given in the paper. [source]

Rotavirus diarrhea in children and adults in a southern city of Brazil in 2003: Distribution of G/P types and finding of a rare G12 strain

JOURNAL OF MEDICAL VIROLOGY, Issue 9 2006
Eduardo Pietruchinski
Abstract Between May and August in 2003, a total of 251 fecal samples were collected from children and adults with diarrhea (5 inpatients and 246 outpatients) at a private hospital in the city of Ponta Grossa, the state of Paraná, Brazil. Group A rotavirus was detected in 71 of 251 (28.3%) specimens: 55 (77.5%) from children under 5 years of age and 16 (22.5%) from individuals aged 6,72 years. All 71 strains exhibited a "long" RNA pattern when analyzed by PAGE. Sixty-one positive samples that yielded enough RNA were submitted to PCR genotyping. The most frequent G/P genotype combination detected was G1P[8] (86.9%; 53/61) followed by G9P[8] (3.3%; 2/61) and G12P[9] (1.6%; 1/61). Rotaviruses with G2, G3, G4, P[4], or P[6] specificity were not detected. For three strains (4.9%) bearing G1 genotype, the VP4 specificity could no be determined, and two specimens (3.3%) remained G/P non-typeable. One rotavirus strain (HC91) bearing G12P[9] genotype with a "long" electropherotype was isolated from an 11-month-old boy with diarrhea for the first time in Brazil. The cell-culture grown HC91 strain was shown to belong to serotype G12 by neutralization. J. Med. Virol. 78:1241,1249, 2006. © 2006 Wiley-Liss, Inc. [source]

Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart Study

DIABETIC MEDICINE, Issue 3 2006
K. P. Burdon
Abstract Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin-angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima-media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population. [source]

ACE and angiotensinogen gene genotypes and left ventricular mass in athletes

Detecting genotype combinations that increase risk for disease: Maternal-Fetal genotype incompatibility test

GENETIC EPIDEMIOLOGY, Issue 1 2003
Janet S. Sinsheimer
Abstract Biological mechanisms that involve gene-by-environment interactions have been hypothesized to explain susceptibility to complex familial disorders. Current research provides compelling evidence that one environmental factor, which acts prenatally to increase susceptibility, arises from a maternal-fetal genotype incompatibility. Because it is genetic in origin, a maternal-fetal incompatibility is one possible source of an adverse environment that can be detected in genetic analyses and precisely studied, even years after the adverse environment was present. Existing statistical models and tests for gene detection are not optimal or even appropriate for identifying maternal-fetal genotype incompatibility loci that may increase the risk for complex disorders. We describe a new test, the maternal-fetal genotype incompatibility (MFG) test, that can be used with case-parent triad data (affected individuals and their parents) to identify loci for which a maternal-fetal genotype incompatibility increases the risk for disease. The MFG test adapts a log-linear approach for case-parent triads in order to detect maternal-fetal genotype incompatibility at a candidate locus, and allows the incompatibility effects to be estimated separately from direct effects of either the maternal or the child's genotype. Through simulations of two biologically plausible maternal-fetal genotype incompatibility scenarios, we show that the type-I error rate of the MFG test is appropriate, that the estimated parameters are accurate, and that the test is powerful enough to detect a maternal-fetal genotype incompatibility of moderate effect size. Genet Epidemiol 24:1,13, 2003. © 2003 Wiley-Liss, Inc. [source]

Resolving Paternity Relationships Using X-Chromosome STRs and Bayesian Networks

JOURNAL OF FORENSIC SCIENCES, Issue 4 2007
Didier Hatsch Ph.D.
Abstract:, X-chromosomal short tandem repeats (X-STRs) are very useful in complex paternity cases because they are inherited by male and female offspring in different ways. They complement autosomal STRs (as-STRs) allowing higher paternity probabilities to be attained. These probabilities are expressed in a likelihood ratio (LR). The formulae needed to calculate LR depend on the genotype combinations of suspected pedigrees. LR can also be obtained by the use of Bayesian networks (BNs). These are graphical representations of real situations that can be used to easily calculate complex probabilities. In the present work, two BNs are presented, which are designed to derive LRs for half-sisters/half-sisters and mother/daughter/paternal grandmother relationships. These networks were validated against known formulae and show themselves to be useful in other suspect pedigree situations than those for which they were developed. The BNs were applied in two paternity cases. The application of the mother/daughter/paternal grandmother BN highlighted the complementary value of X-STRs to as-STRs. The same case evaluated without the mother underlined that missing information tends to be conservative if the alleged father is the biological father and otherwise nonconservative. The half-sisters case shows a limitation of statistical interpretations in regard to high allelic frequencies. [source]

Polymorphisms of Alcohol Dehydrogenase-1B and Aldehyde Dehydrogenase-2 and the Blood and Salivary Ethanol and Acetaldehyde Concentrations of Japanese Alcoholic Men

ALCOHOLISM, Issue 7 2010
Akira Yokoyama
Background:, The effects of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) on alcohol metabolism are striking in nonalcoholics, and the effects of genetic polymorphism of alcohol dehydrogenase-1B (ADH1B) are modest at most, whereas genetic polymorphisms of both strongly affect the susceptibility to alcoholism and upper aerodigestive tract (UADT) cancer of drinkers. Methods:, We evaluated associations between ADH1B/ADH1C/ALDH2 genotypes and the blood and salivary ethanol and acetaldehyde levels of 168 Japanese alcoholic men who came to our hospital for the first time in the morning and had been drinking until the day before. Results:, The ethanol levels in their blood and saliva were similar, but the acetaldehyde levels in their saliva were much higher than in their blood, probably because of acetaldehyde production by oral bacteria. Blood and salivary ethanol and acetaldehyde levels were both significantly higher in the subjects with the less active ADH1B*1/*1 genotype than in the ADH1B*2 carriers, but none of the levels differed according to ALDH2 genotype. Significant linkage disequilibrium was detected between the ADH1B and ADH1C genotypes, but ADH1C genotype did not affect the blood or salivary ethanol or acetaldehyde levels. High blood acetaldehyde levels were found even in the active ALDH2*1/*1 alcoholics, which were comparable with the levels of the inactive heterozygous ALDH2*1/*2 alcoholics with less active ADH1B*1/*1. The slope of the increase in blood acetaldehyde level as the blood ethanol level increased was significantly steeper in alcoholics with inactive heterozygous ALDH2*1/*2 plus ADH1B*2 allele than with any other genotype combinations, but the slopes of the increase in salivary acetaldehyde level as the salivary ethanol level increased did not differ between the groups of subjects with any combinations of ALDH2 and ADH1B genotypes. Conclusions:, The ADH1B/ALDH2 genotype affected the blood and salivary ethanol and acetaldehyde levels of nonabstinent alcoholics in a different manner from nonalcoholics, and clear effects of ADH1B genotype and less clear effects of ALDH2 were observed in the alcoholics. Alterations in alcohol metabolism as a result of alcoholism may modify the gene effects, and these findings provide some clues in regard to associations between the genotypes and the risks of alcoholism and UADT cancer. [source]

Polymorphisms of the human platelet alloantigens HPA-1, HPA-2, HPA-3, and HPA-4 in ischemic stroke

AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2008
Sarra Saidi
Polymorphism in human platelet antigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa), and HPA-5 (GPIa/IIa) was investigated in 329 stroke patients and 444 matched control subjects. HPA genotyping was done by PCR-SSP method. Lower HPA-1a (P < 0.001) and higher HPA-1b (P < 0.001) allele frequencies were seen in patients than control subjects, and homozygosity for HPA-1b (P < 0.001) alleles was more prevalent in stroke cases than in controls. The allele and genotype distributions of the other HPA polymorphic variants were similar between cases and controls. Select HPA combined genotypes comprising the 2121 (Pc = 0.008) and 2221 (Pc = 0.018) genotypes, which were positively associated, and the 1111 (Pc < 0.001), which was negatively associated with stroke, thereby conferred a disease susceptibility and protective nature to these genotype combinations. Multivariate analysis confirmed the negative association of the 1111 (P < 0.001) and the positive association of the 2121 (P = 0.017) combined genotypes with stroke, after adjustment for a number of covariates. This is the first evidence demonstrating differential association of the common 4 HPA gene variants and specific HPA genotype combinations with stroke. Am. J. Hematol. 2008. © 2008 Wiley-Liss, Inc. [source]

Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome

CLINICAL ENDOCRINOLOGY, Issue 1 2006
Nicole Draper
Summary Objective, There are close phenotypic similarities between cortisone reductase deficiency (CRD), a rare abnormality of cortisone metabolism, and polycystic ovary syndrome (PCOS). As there is evidence that CRD results from digenic mutations involving the genes encoding 11,-hydroxysteroid dehydrogenase type 1 (HSD11B1) and hexose-6-phosphate dehydrogenase (H6PD), we sought to establish whether CRD-associated variants in these genes, individually or in combination, influence susceptibility to PCOS. Design, Case-control, family-based association and quantitative-trait analyses. Patients, A UK case sample comprising 256 nuclear families ascertained from a PCOS offspring and 213 singleton PCOS cases plus 549 control subjects. Measurements, All subjects were genotyped for CRD-related variants in HSD11B1 (rs12086634) and H6PD (rs6688832). Testosterone was measured with an in-house radioimmunoassay using ether extraction and dextran-coated charcoal separation. Results, Case-control analyses revealed no differences in genotype distribution between PCOS and controls for rs12086634 or rs6688832 (both P = 0·84). Three per cent of cases and 2·4% of controls had genotype combinations (three or more variant alleles at the two sites) considered characteristic of CRD (P = 0·73). There were no departures from expectation in the family-based association studies, and no significant associations between genotypes (individually or in combination) and BMI, WHR or testosterone. Conclusions, The variants in HSD11B1 and H6PD typed, though implicated in causation of CRD, do not influence susceptibility to PCOS. It seems likely that additional variants within these genes are required for the development of CRD. [source]