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Protective Allele (protective + allele)
Selected AbstractsOpposite gene by environment interactions in Karelia for CD14 and CC16 single nucleotide polymorphisms and allergyALLERGY, Issue 9 2009G. Zhang Background:, Finnish Karelians have a higher prevalence of allergic disease than Russian Karelians. As both populations are generally from the same ethnic group, the Karelian population offers a unique opportunity to analyse genetic and allergic disease interactions between ,Western' and ,Eastern' environments. Objectives:, We investigated associations between allergic diseases and CD14 and CC16 polymorphisms in Finnish vs Russian Karelian women. Methods:, Adult female Karelians (330 Finnish and 274 Russian) were recruited, examined for a range of symptoms and conditions including rhinitis, itchy rash, asthma and atopy and genotyped for CD14 C-159T and CC16 A38G. Results:, For both CD14 C-159T and CC16 A38G, the risk allele for atopic phenotypes in Finnish Karelia was the protective allele in Russian Karelia. For CD14 C-159T, an interactive effect on ever itchy rash (Pinteraction = 0.004), itchy rash <12 mo (Pinteraction = 0.001) and dry cough at night in the past 12 months (<12 months) (Pinteraction = 0.011) was found; the risk allele was C in Russians and T in Finns. For CC16 A38G, an interaction was significant for ever rhinitis (Pinteraction = 0.006), rhinitis <12 mo (Pinteraction = 0.004), and marginally significant for ever hayfever (Pinteraction = 0.07), allergic eye symptoms <12 mo (Pinteraction = 0.09); their risk allele was G in Russians and A in Finns. Conclusion:, An Eastern vs Western environment appears to exert an effect via opposite alleles on risk of allergic diseases in adult women. [source] Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate carcinomaTHE PROSTATE, Issue 6 2010Jessica Lubahn Abstract BACKGROUND Because of the dramatically different clinical course of aggressive and indolent prostate carcinoma (PCa), markers that distinguish between these phenotypes are of critical importance. Apoptosis is an important protective mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction in this pathway is a key step in cancer progression. As such, genetic variants in apoptosis genes are potential markers of aggressive PCa. Recent work in breast carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a protective risk allele. METHODS We tested the hypothesis that the H variant was protective for aggressive PCa in a pooled analysis of 796 aggressive cases and 2,060 controls. RESULTS The H allele was associated with a reduced risk of aggressive PCa (ORper allele,= 0.67, 95% CI: 0.54,0.83, Ptrend,=,0.0003). The results were similar for European-Americans (ORper allele,=,0.68; 95% CI: 0.54,0.86) and African-Americans (ORper allele,=,0.61; 95% CI: 0.34,1.10). We further determined from the full series of 1,160 cases and 1,166 controls in the Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect of the H allele tended to be limited to high-grade and advanced PCa (all cases ORper allele,=,0.94; 95% CI: 0.79,1.11; localized, low-grade disease ORper allele,=,0.98; 95% CI: 0.79,1.23; and aggressive disease ORper allele,=,0.73; 95% CI: 0.50,1.07). CONCLUSION These results suggest that histidine variant of CASP8 D302H is a protective allele for aggressive PCa with potential utility for identification of patients at differential risk for this clinically significant phenotype. Prostate 70: 646,653, 2010. © 2009 Wiley-Liss, Inc. [source] Protection against anti,citrullinated protein antibody,positive rheumatoid arthritis is predominantly associated with HLA,DRB1*1301: A meta-analysis of HLA,DRB1 associations with anti,citrullinated protein antibody,positive and anti,citrullinated protein antibody,negative rheumatoid arthritis in four European populationsARTHRITIS & RHEUMATISM, Issue 5 2010Diane van der Woude Objective The protective effect of HLA,DRB1 alleles on the development of rheumatoid arthritis (RA) is poorly understood. The aim of this study was to perform a meta-analysis of 4 European populations to investigate which HLA,DRB1 alleles are associated with protection in anti,citrullinated protein antibody (ACPA),positive RA and ACPA-negative RA. Methods Data for >2,800 patients and >3,000 control subjects for whom information on HLA,DRB1 typing and ACPA status was available were collected from 4 European countries: Norway, Sweden, The Netherlands, and Spain. The odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with the different HLA,DRB1 alleles were analyzed in a combined meta-analysis focused on protective alleles and classifications. The analysis of ACPA-positive RA was stratified for the shared epitope (SE) alleles, to correct for skewing due to this association. Results In ACPA-positive RA, the only alleles that conveyed protection after stratification for SE were HLA,DRB1*13 alleles (OR 0.54 [95% CI 0.38,0.77]). The protective effect of the allele classifications based on the DERAA and D70 sequences was no longer present after exclusion of DRB1*13 (for D70, OR 0.97 [95% CI 0.75,1.25]), indicating that DRB1*13, rather than the DERAA or D70 sequence as such, is associated with protection. Among the DRB1*13 alleles, only DRB1*1301 was associated with protection (OR 0.24 [95% CI 0.09,0.59]). Protection appeared to follow a north-to-south gradient, with the strongest association in northern European countries. In ACPA-negative RA, there were no robust associations with HLA,DRB1 alleles. Conclusion Our data do not support any of the classifications of protective alleles and indicate that protection against ACPA-positive RA is predominantly associated with HLA,DRB1*1301. [source] A new classification of HLA,DRB1 alleles differentiates predisposing and protective alleles for rheumatoid arthritis structural severityARTHRITIS & RHEUMATISM, Issue 2 2006Pierre-Antoine Gourraud Objective A new classification of HLA,DRB1 alleles supporting the shared epitope hypothesis of rheumatoid arthritis (RA) susceptibility was recently introduced. We investigated the relevance of this classification in terms of the structural severity of RA. Methods The study group comprised 144 patients who were included in a prospective longitudinal cohort of French Caucasoid patients with early RA. Progression of the total radiographic damage score (Sharp/van der Heijde method) was used to quantify the structural severity of RA after 4 years of followup. HLA,DRB1 typing and subtyping were performed by polymerase chain reaction, using a panel of sequence-specific oligonucleotide probes. HLA,DRB1 alleles were classified according to the above-mentioned new system. The association between the HLA,DRB1 allele groups (S1, S2, S3P, S3D, and X) and the structural severity of RA was analyzed with nonparametric statistical tests. Results The presence of S2 alleles (HLA,DRB1*0401 and HLA,DRB1*1303) was associated with severe forms of RA (P = 0.004); a significant dose effect was observed (P = 0.01). The presence of S3D alleles (HLA,DRB1*11001, HLA,DRB1*1104, HLA,DRB1*12, and HLA,DRB1*16) was associated with benign forms of RA (P < 0.0001), and a significant dose effect was observed (P < 0.01). Conclusion The studied classification of HLA,DRB1 alleles is relevant in terms of RA outcomes. Compared with a previously described classification system, this system differentiates predisposing (S2) and protective (S3D) alleles for RA structural severity, which, respectively, correspond to KRRAA and DRRAA amino acid patterns at position 70,74 of the third hypervariable region of the HLA,DR, chain. [source] | ||||||||||