A common functional variant in the interleukin-6 gene is associated with increased body mass index in subjects with type 2 diabetes mellitus

Circulating levels of interleukin-6 (IL-6) are raised in insulin resistant states such as obesity, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). Growing evidence suggests that IL-6 is not only produced by fat cells but is also capable of inducing insulin resistance in these...

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Bibliographic Details
Published in:Molecular genetics and metabolism 2004-06, Vol.82 (2), p.180-186
Main Authors: Stephens, Jeffrey W, Hurel, Steven J, Cooper, Jacqueline A, Acharya, Jayshree, Miller, George J, Humphries, Steve E
Format: Article
Language:English
Subjects:
Body Mass Index
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - physiopathology
European Continental Ancestry Group
Genetic Predisposition to Disease
Genetic Variation - genetics
Humans
Interleukin-6 - genetics
Male
Middle Aged
United Kingdom
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Summary:Circulating levels of interleukin-6 (IL-6) are raised in insulin resistant states such as obesity, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). Growing evidence suggests that IL-6 is not only produced by fat cells but is also capable of inducing insulin resistance in these cells. The expected result of this in vivo, would be to increase adipose mass and subsequently body mass index (BMI). The IL-6 −174G > C common functional gene variant has consistently been associated with increased plasma IL-6, insulin resistance, and increased cardiovascular risk. We looked at the association between genotype and BMI in 571 Caucasian subjects with T2DM. There was a significant linear association between genotype and BMI: Median (interquartile range) GG 28.8 kg/m 2 (26.0–31.6) vs GC; 29.4 kg/m 2 (26.3–32.5) vs CC; 30.4 kg/m 2 (26.1–33.0), p=0.05. When the group was divided by the median BMI (29.1 kg/m 2), 62% of −174CC subjects were in the higher group compared to 38% in the lower group ( p=0.008). By contrast, in 2652 non-diabetic Caucasian men with a median BMI of 26.1 kg/m 2, there was no difference in genotype distribution ( p=0.288). The frequency of the −174C allele was lower in type 2 diabetes compared to the non-diabetic men (−174C allele frequency: 0.35[0.33–0.38] vs 0.43[0.42–0.45], p
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2004.04.001