Mutation screening and association of human retinoid X receptor γ variation with lipid levels in familial type 2 diabetes

• Published in: Molecular genetics and metabolism 2002-05, Vol.76 (1), p.14-22
• Main Authors: Wang, Hua, Chu, Winston, Hemphill, Christopher, Hasstedt, Sandra J., Elbein, Steven C.
• Format: Article
• Language: English
• Subjects: Blood Glucose - metabolism; Cholesterol, HDL - blood; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Fatty Acids, Nonesterified - blood; Free fatty acids; Glucose tolerance; Haplotypes; Humans; Insulin - blood; Linkage Disequilibrium; Lipid metabolism; Mutation; Polymorphism; Polymorphism, Single Nucleotide; Receptors, Retinoic Acid - genetics; Retinoid X receptor; Retinoid X Receptors; Sequence Analysis, DNA; Transcription Factors - genetics; Triglycerides; Triglycerides - blood; Type 2 diabetes
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/S1096-7192(02)00016-1

Both type 2 diabetes (T2DM) and familial combined hyperlipidemia have been mapped to human chromosome 1q21–q24. This region includes the retinoid X receptor γ (RXR γ) , which is a strong candidate for both glucose and lipid metabolism. Retinoid X receptors form heterodimers with a variety of nuclear receptors, including peroxisome-proliferator-activated receptors α and γ ( PPARα and PPARγ), and are synergistic targets for drugs that alter glucose and lipid metabolism. We hypothesized that RXRγ variation could explain the linkage of diabetes and lipid disorders to this region. We screened each of the 10 exons, the flanking intronic sequences, the 3 ′ untranslated region, and the 5 ′ flanking region. We identified 14 variants, none of which altered the coding sequence. Of the 10 variants examined in a diabetes case-control study, three showed nominal ( p