Variation in the Interleukin-6 Receptor Gene Associates With Type 2 Diabetes in Danish Whites
Yasmin H. Hamid 1 ,
Søren A. Urhammer 1 ,
Dorit P. Jensen 1 ,
Charlotte Glümer 1 2 ,
Knut Borch-Johnsen 1 3 ,
Torben Jørgensen 2 ,
Torben Hansen 1 and
Oluf Pedersen 1 3
1 Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Copenhagen, Denmark
2 Research Centre for Prevention and Health, Copenhagen County, Glostrup University Hospital, Glostrup, Denmark
3 Faculty of Health Science, University of Aarhus, Aarhus, Denmark
Address correspondence and reprint requests to Yasmin Hassan Hamid, MD, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820
Gentofte, Copenhagen, Denmark. E-mail: yah{at}steno.dk
Abstract
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 α-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.
IFG, impaired fasting glucose
IGT, impaired glucose tolerance
IL-6, interleukin-6
IL6R, IL-6 receptor
OGTT, oral glucose tolerance test
NGT, normal glucose tolerance
sIL6R, soluble IL6R
SNP, single nucleotide polymorphism
Footnotes
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org .
Accepted August 30, 2004.
Received June 3, 2004.
DIABETES...

Variation in the Interleukin-6 Receptor Gene Associates With Type 2 Diabetes in Danish Whites

10.2337/diabetes.53.12.3342