Journal
MOLECULAR GENETICS AND METABOLISM
Volume 87, Issue 1, Pages 54-60Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymgme.2005.07.013
Keywords
opioid receptor; association; positional cloning; type 2 diabetes; haplotype; African American
Funding
- NIDDK NIH HHS [R01 DK066358, R01 DK53591] Funding Source: Medline
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK066358, R01DK053591] Funding Source: NIH RePORTER
Ask authors/readers for more resources
African Americans (AA) are at increased risk for developing type 2 diabetes mellitus (T2DM) relative to European Americans. We previously detected linkage of T2DM to 6q24-q27 (LOD 2.26) at 163.5 cM, closest to marker D6S1035, in a genome-wide scan of AA families. The mu-opioid receptor gene (OPRM1) is located within the LOD-1 support interval of this linkage peak. OPRM1 is an attractive positional candidate gene for T2DM susceptibility since agonists of OPRM1 affect glucose-induced insulin release and OPRM1 knockout mice have a more rapid induction of insulin resistance than wild-type. Twenty-two SNPs in this gene, at an average spacing of 3.9kb, were genotyped in 380 AA T2DM cases and 276 AA controls. In single SNP association analyses, rs648007 demonstrated significant evidence of association with T2DM (P = 0.0 13). Four blocks of high linkage disequilibrium were detected across the OPRM1 gene. Association analyses of haplotypes in each of these blocks revealed two haplotype blocks with significant overall P values (P = 0.007 and 0.046). Significant, but rare, risk and protective haplotypes were identified as driving these associations with T2DM (P = 0.034-0.047). These associations suggest that the OPRM1 gene plays a role in T2DM susceptibility in African Americans. (c) 2005 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available