TY - JOUR

T1 - The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 diabetes mellitus in Native Americans and Caucasians

AU - Vozarova, Barbora

AU - Fernández-Real, José-Manuel

AU - Knowler, William C

AU - Gallart, Lluis

AU - Hanson, Robert L

AU - Gruber, Jonathan D

AU - Ricart, Wilfredo

AU - Vendrell, Joan

AU - Richart, Cristóbal

AU - Tataranni, P Antonio

AU - Wolford, Johanna K

AU - de Courten, Barbora

PY - 2003/4/1

Y1 - 2003/4/1

N2 - Chronic low-grade activation of the immune system may play a role in the pathogenesis of type-2 diabetes mellitus (T2DM). Interleukin-6 (IL6), a powerful inducer of hepatic acute phase response, has been implicated in the etiology of insulin resistance and T2DM. Recently, an IL6 promoter polymorphism (G/C) at position -174 was found to be associated with measures of insulin sensitivity. Because we have previously found an association between high IL6 levels and insulin resistance in both Pima Indians - a population with high rates of insulin resistance and T2DM - and Caucasians, we aimed to assess whether the IL6 promoter polymorphism is associated with T2DM in these populations. We genotyped the IL6 (-174) G/C polymorphism using pyrosequencing in 463 Native Americans and by PCR-RFLP in 329 Spanish Caucasians. Among the Spanish Caucasian subjects, there was a significant difference in genotypic distribution between diabetic and non-diabetic subjects (P=0.028); the GG genotype was more common in diabetic (0.40) than in non-diabetic (0.29) subjects. The G allele was much more frequent in the Native American sample, and among a sample of 143 cases and 145 controls, the GG genotype was significantly more common in diabetic subjects (P=0.019). When this sample population was stratified according to ethnic heritage, all 211 subjects who were of full Pima Indian heritage had the GG genotype, whereas in the 77 American Indian subjects with non-Pima admixture, T2DM was associated with IL6 genotype (P=0.001). These findings are consistent with a role for genetic determinants of inflammation in the development of T2DM in both Native Americans and Caucasians.

AB - Chronic low-grade activation of the immune system may play a role in the pathogenesis of type-2 diabetes mellitus (T2DM). Interleukin-6 (IL6), a powerful inducer of hepatic acute phase response, has been implicated in the etiology of insulin resistance and T2DM. Recently, an IL6 promoter polymorphism (G/C) at position -174 was found to be associated with measures of insulin sensitivity. Because we have previously found an association between high IL6 levels and insulin resistance in both Pima Indians - a population with high rates of insulin resistance and T2DM - and Caucasians, we aimed to assess whether the IL6 promoter polymorphism is associated with T2DM in these populations. We genotyped the IL6 (-174) G/C polymorphism using pyrosequencing in 463 Native Americans and by PCR-RFLP in 329 Spanish Caucasians. Among the Spanish Caucasian subjects, there was a significant difference in genotypic distribution between diabetic and non-diabetic subjects (P=0.028); the GG genotype was more common in diabetic (0.40) than in non-diabetic (0.29) subjects. The G allele was much more frequent in the Native American sample, and among a sample of 143 cases and 145 controls, the GG genotype was significantly more common in diabetic subjects (P=0.019). When this sample population was stratified according to ethnic heritage, all 211 subjects who were of full Pima Indian heritage had the GG genotype, whereas in the 77 American Indian subjects with non-Pima admixture, T2DM was associated with IL6 genotype (P=0.001). These findings are consistent with a role for genetic determinants of inflammation in the development of T2DM in both Native Americans and Caucasians.

KW - Adult

KW - Aged

KW - Alleles

KW - Asian Continental Ancestry Group

KW - Case-Control Studies

KW - Cytosine

KW - Diabetes Mellitus, Type 2

KW - European Continental Ancestry Group

KW - Female

KW - Genotype

KW - Guanine

KW - Hispanic Americans

KW - Humans

KW - Indians, North American

KW - Interleukin-6

KW - Male

KW - Middle Aged

KW - Polymerase Chain Reaction

KW - Polymorphism, Genetic

KW - Polymorphism, Restriction Fragment Length

KW - Promoter Regions, Genetic

U2 - 10.1007/s00439-003-0912-x

DO - 10.1007/s00439-003-0912-x

M3 - Journal article

C2 - 12589429

VL - 112

SP - 409

EP - 413

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 4

ER -