BACKGROUND: Type 1 diabetes (T1D) is a multifactorial disease, the genetic analysis of which has yielded few true positive linkage and association results. Replication of association in independent, large-sample studies is essential to further identify the genes involved in T1D. Two single nucleotide polymorphisms (SNPs) in the catalase gene have been reported to be associated with T1D. METHODS: Major effects of two SNPs, C1167T (rs769217) and C(-262)T (rs1001179), of the catalase gene on T1D susceptibility have been reported previously in Russians from Moscow. We genotyped C1167T and C(-262)T in large family (1642 families) and British case-control (3530 cases and 3930 controls) collections and tested for association with T1D. RESULTS: We found no evidence of an association between T1D and C1167T or C(-262)T in either the family or case-control collections, or for the D11S2008 microsatellite polymorphism in families. However, we did find limited statistical evidence of an association at C1167T in USA families (P = 0.033; RR for 1167C = 1.23, 95% CI = 1.02-1.49) and C(-262)T in UK families (P = 0.046; RR for (-262)C = 0.86, 95% CI = 0.75-0.99). CONCLUSION: We found no evidence for a major effect of C1167T or C(-262)T on T1D susceptibility in two large sample collections. Limited statistical evidence of an association at C1167T in USA families and C(-262)T in UK families was found, but these results are likely to be false positives. The previously reported association of these SNPs may also have been a false positive, or a population specific association in Russians from Moscow.
BACKGROUND: Type 1 diabetes (T1D) is a multifactorial disease, the genetic analysis of which has yielded few true positive linkage and association results. Replication of association in independent, large-sample studies is essential to further identify the genes involved in T1D. Two single nucleotide polymorphisms (SNPs) in the catalase gene have been reported to be associated with T1D. METHODS: Major effects of two SNPs, C1167T (rs769217) and C(-262)T (rs1001179), of the catalase gene on T1D susceptibility have been reported previously in Russians from Moscow. We genotyped C1167T and C(-262)T in large family (1642 families) and British case-control (3530 cases and 3930 controls) collections and tested for association with T1D. RESULTS: We found no evidence of an association between T1D and C1167T or C(-262)T in either the family or case-control collections, or for the D11S2008 microsatellite polymorphism in families. However, we did find limited statistical evidence of an association at C1167T in USA families (P = 0.033; RR for 1167C = 1.23, 95% CI = 1.02-1.49) and C(-262)T in UK families (P = 0.046; RR for (-262)C = 0.86, 95% CI = 0.75-0.99). CONCLUSION: We found no evidence for a major effect of C1167T or C(-262)T on T1D susceptibility in two large sample collections. Limited statistical evidence of an association at C1167T in USA families and C(-262)T in UK families was found, but these results are likely to be false positives. The previously reported association of these SNPs may also have been a false positive, or a population specific association in Russians from Moscow.
Authors: Julie M Cunningham; Thomas A Sellers; Joellen M Schildkraut; Zachary S Fredericksen; Robert A Vierkant; Linda E Kelemen; Madhura Gadre; Catherine M Phelan; Yifan Huang; Jeffrey G Meyer; V Shane Pankratz; Ellen L Goode Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-07 Impact factor: 4.254