Polymorphisms in the Oxygen-Regulated Protein 150 Gene (ORP150) Are Associated With Insulin Resistance in Pima Indians
- From the Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Phoenix, Arizona
Abstract
The ORP150 gene that encodes the human oxygen-regulated protein (150 kDa) maps to chromosome 11q23, a region previously reported to be linked to type 2 diabetes and obesity in Pima Indians. This gene was also found to be differentially expressed in global gene expression studies comparing muscle mRNA from insulin-resistant versus insulin-sensitive subjects. Therefore, ORP150 was analyzed as a candidate gene for susceptibility to diabetes. Twelve variants were identified, and three unique representative polymorphisms were genotyped in 1,338 Pima Indians. None of these polymorphisms were associated with diabetes, but two polymorphisms were significantly associated with measures of insulin resistance. These data indicate that ORP150 has a role in insulin action but does not have a major role in determining susceptibility to type 2 diabetes in Pima Indians.
Footnotes
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Address correspondence and reprint requests to Leslie J. Baier, Clinical Diabetes and Nutrition Section, NIDDK, NIH, 4212 N. 16th St., Phoenix, AZ 85016. E-mail: lbaier{at}phx.niddk.nih.gov.
Received for publication 18 December 2001 and accepted in revised form 5 February 2002.
ER, endoplasmic reticulum; EST, expressed sequence tag; GRP, glucose-regulated protein; LOD, logarithm of odds; ORP, oxygen-regulated protein; SNP, single nucleotide polymorphism.
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