title: Analysis of polymorphisms of the interleukin-18 gene in type 1 diabetes and Hardy-Weinberg equilibrium testing.
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.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, UK.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Szeszko
authors.forename: Joanna M M
authors.initials: JM
authors.lastname: Howson
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Neil M
authors.initials: NM
authors.lastname: Walker
authors.forename: Rebecca C J
authors.initials: RC
authors.lastname: Twells
authors.forename: Helen E
authors.initials: HE
authors.lastname: Stevens
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Nutland
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D020382:Interleukin-18