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Analysis of polymorphisms of the interleukin-18 gene in type 1 diabetes and Hardy-Weinberg equilibrium testing

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Abstract

Recently, the interleukin-18 cytokine gene (IL18) was reported to be associated with type 1 diabetes. In the present report, we calculated that the reported genotypes of the two 5′ region/promoter single nucleotide polymorphisms (SNPs), -607 (C→A) (rs1946518) and -137 (G→C) (rs187238), were not in Hardy-Weinberg equilibrium (HWE). We therefore investigated the association of the -607 and -137 SNPs in a U.K. type 1 diabetic Caucasian case-control collection (1,560 case and 1,715 control subjects tested at -607 and 4,323 case and 4,610 control subjects tested at -137) as well as a type 1 diabetic Caucasian collection comprised of families of European ancestry (1,347 families tested at -137 and 1,356 families tested at -607). No evidence for association with type 1 diabetes was found, including for the -607 A/A and C/A genotypes. To evaluate whether common variation elsewhere in the gene was associated with disease susceptibility, we analyzed eight IL18 tag SNPs in a type 1 diabetic case-control collection (1,561 case and 1,721 control subjects). No evidence for association was obtained (P = 0.11). We conclude that common allelic variation in IL18 is unlikely to contribute substantially to type 1 diabetes susceptibility in the populations tested and recommend routine application of tests for HWE in population-based studies for genetic association. © 2006 by the American Diabetes Association.

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Szeszko, J. S., Howson, J. M. M., Cooper, J. D., Walker, N. M., Twells, R. C. J., Stevens, H. E., … Todd, J. A. (2006). Analysis of polymorphisms of the interleukin-18 gene in type 1 diabetes and Hardy-Weinberg equilibrium testing. Diabetes, 55(2), 559–562. https://doi.org/10.2337/diabetes.55.02.06.db05-0826

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