Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians

Insulin resistance is strongly associated with obesity, but even among obese subjects insulin sensitivity varies widely. Recently, a new adipocyte hormone, resistin, was identified, shown to reduce insulin-mediated glucose uptake, and shown to be increased in obese mice. We used the chromosome 19 dr...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2002-06, Vol.87 (6), p.2520-2524
Main Authors: Wang, Hua, Chu, Winston S, Hemphill, Chris, Elbein, Steven C
Format: Article
Language:English
Subjects:
Base Sequence - genetics
Body Mass Index
Chromosomes, Human, Pair 19 - genetics
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - pathology
European Continental Ancestry Group - genetics
Female
Genetic Testing
Humans
Insulin Resistance - genetics
Intermediate Filament Proteins - genetics
Male
Microsatellite Repeats
Microtubule-Associated Proteins
Neoplasm Proteins - genetics
Obesity - genetics
Polymorphism, Genetic - physiology
Promoter Regions, Genetic - genetics
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Summary:Insulin resistance is strongly associated with obesity, but even among obese subjects insulin sensitivity varies widely. Recently, a new adipocyte hormone, resistin, was identified, shown to reduce insulin-mediated glucose uptake, and shown to be increased in obese mice. We used the chromosome 19 draft sequence to determine the genomic structure of human resistin and to screen the exons, introns, and flanking sequences for variation. We screened 44 subjects with type 2 diabetes and 20 nondiabetic family members who were at the extremes of insulin sensitivity. We identified eight noncoding single nucleotide polymorphisms (SNPs) and one GAT microsatellite repeat. Three SNPs, which were in incomplete linkage disequilibrium with each other and had allelic frequencies exceeding 5%, were selected for further study. No SNP was associated with type 2 diabetes, but the SNP in the promoter region was a significant determinant of insulin sensitivity index (P = 0.04) among nondiabetic family members who had undergone iv glucose tolerance tests. The three common SNPs showed statistical significance as determinants of insulin sensitivity index (P < 0.01) in interaction with body mass index. Noncoding SNPs in the resistin gene may influence insulin sensitivity in interaction with obesity, but this finding will need to be confirmed in other populations.
ISSN:0021-972X
DOI:10.1210/jc.87.6.2520