Interleukin-6-174 G > C polymorphism affects the association between IL-6 plasma levels and insulin resistance in type 2 diabetic patients.
Interleukin-6 (IL-6), a powerful inflammatory mediator, plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Recently, the IL-6 promoter polymorphism, at position -174 (G > C), has been associated to insulin sensitivity although contrasting data have been reported. The aim of this study was to evaluate the effect of the IL-6-174 G > C polymorphism on insulin resistance. In 238 type 2 diabetic patients without diabetic complications and in 255 control subjects, age and gender-matched, we evaluated the IL-6 -174 G > C genotype, the IL-6 plasma levels and the insulin resistance by the homeostasis model assessment (HOMA). The levels of IL-6 and HOMA were not genotype-dependent and were higher in diabetic patients (p < 0.01). Control subjects, both C+ (CG + CC genotypes) and C- (GG genotype) carriers, showed IL-6 plasma levels significantly related to BMI, fasting insulin and HOMA. The same relationships were found in C+ diabetic carriers. Differently, diabetic C- carriers did not show any relationship between IL-6 levels and all the evaluated variables. Interestingly, all the correlations were dependent on BMI. These findings highlight that IL-6-174 G > C polymorphism affects insulin resistance in type 2 diabetes, where C+ carriers have an insulin resistance "IL-6-sensitive", while C- carriers do not. The identification of two categories of diabetic patients may, therefore, lead to different therapeutic strategies in the management of insulin resistance.
Testa
R
R
Diabetology Unit, INRCA, Via Della Montagnola, 81, I-60131, Ancona, Italy. r.testa@inrca.it
Olivieri
F
F
Bonfigli
A R
AR
Sirolla
C
C
Boemi
M
M
Marchegiani
F
F
Marra
M
M
Cenerelli
S
S
Antonicelli
R
R
Dolci
A
A
Paolisso
G
G
Franceschi
C
C
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology*; D005215:Fasting; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6