Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites.
Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the pathophysiology of various human diseases such as type 2 diabetes and obesity. IL-6 signals via a heterodimeric receptor complex consisting of a soluble IL-6 alpha-subunit (IL-6 receptor [IL6R]) and a signal transducing subunit (gp130). The IL6R gene maps to an important candidate locus for type 2 diabetes on chromosome 1q21. An Asp358Ala polymorphism of the IL6R has been reported to associate with obesity in Pima Indians. We investigated the Asp358Ala polymorphism in relation to type 2 diabetes, obesity, and other pre-diabetic quantitative traits among Danish whites. By applying a recessive genetic model in a case-control study of 1,349 type 2 diabetic patients and 4,596 glucose-tolerant control subjects, we found a significant difference in genotype distribution (P = 0.008) and in allele frequency (Ala-allele 38.3% [95% CI 36.5-40.1] in diabetic subjects vs. 41.2% [40.2-42.2] in control subjects; P = 0.007). The odds ratio for the Asp/Asp carriers versus Ala/Ala carriers was 1.38 (1.09-1.71). Among 4,251 middle-aged glucose-tolerant subjects, the Asp358Ala polymorphism was not associated with estimates of obesity, post-oral glucose tolerance test serum insulin release, or the homeostasis model assessment of insulin resistance index. In conclusion, the Asp358Ala polymorphism of the IL6R associates with type 2 diabetes in Danish whites.
Hamid
Yasmin H
YH
Steno Diabetes Center, Hagedorn Research Institute, Gentofte, Copenhagen, Denmark. yah@steno.dk
Urhammer
Søren A
SA
Jensen
Dorit P
DP
Glümer
Charlotte
C
Borch-Johnsen
Knut
K
Jørgensen
Torben
T
Hansen
Torben
T
Pedersen
Oluf
O
D019943:Amino Acid Substitution; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D044465:White People / Q000235:genetics*
D019947:Receptors, Interleukin-6