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Diabetes. 2010 Aug;59(8):2080-5. doi: 10.2337/db09-1593. Epub 2010 Jun 3.

Functional variants in MBL2 are associated with type 2 diabetes and pre-diabetes traits in Pima Indians and the old order Amish.

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  • 1Diabetes Molecular Genetics Section and, Diabetes Epidemiology, the National Institute of Diabetes and Digestive andKidney Disease, the National Institutes of Health, Phoenix, Arizona, USA.

Abstract

OBJECTIVE:

MBL2 encodes the mannose-binding lectin, which is a key player in the innate immune system and has recently been found to play a role in insulin resistance and development of type 1 diabetes and gestational diabetes mellitus. To assess the role of MBL2 in diabetes susceptibility, this gene was analyzed in the Pima Indian population, which has a high prevalence of type 2 diabetes.

RESEARCH DESIGN AND METHODS:

Nineteen tag single nucleotide polymorphisms (SNPs) were genotyped in a population-based sample of 3,501 full-heritage Pima Indians, and selected SNPs were further genotyped in independent samples of Native American (n = 3,723) and Old Order Amish (n = 486) subjects.

RESULTS:

Two variants, a promoter SNP (rs11003125) at -550 bp with a risk allele frequency of 0.77 and a Gly54Asp (rs1800450) with a risk allele frequency of 0.83, were associated with type 2 diabetes in the full-heritage Pima Indians (odds ratio 1.30 per copy of the G allele for rs1103125, P = 0.0007, and 1.30 per copy of the glycine allele for rs1800450, P = 0.002, adjusted for age, sex, birth year, and family membership). These associations replicated in an independent Native American sample (1.19, P = 0.04, for rs11003125) and a Caucasian sample, the Old Order Amish (1.51, P = 0.004, for rs1103125 and 2.38, P = 0.003, for rs1800450). Among Pima Indians with normal glucose tolerance, the diabetes risk allele glycine of Gly54Asp was associated with a decreased acute insulin response to an intravenous glucose bolus infusion (P = 0.004, adjusted for age, sex, percent body fat, glucose disposal under physiological insulin stimulation, and family membership).

CONCLUSIONS:

Our data suggest that the functional variants in MBL2 contribute to type 2 diabetes susceptibility in both Native Americans and the Old Order Amish.

PMID:
20522590
[PubMed - indexed for MEDLINE]
PMCID:
PMC2911048
Free PMC Article
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