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- Title
Identification of polymorphic loci in the promoter region of the serotonin 5-HT<sub>2C</sub> receptor gene and their association with obesity and Type II diabetes.
- Authors
Yuan, X.; Yamada, K.; Ishiyama-Shigemoto, S.; Koyama, W.; Nonaka, K.
- Abstract
Aims/hypothesis. Polymorphisms in the upstream region of the 5-HT2C receptor gene could play a part in the development of obesity.¶Methods. We screened the upstream region from 27 men by the single strand conformational polymorphism analysis and PCR-direct sequencing and then genotyped 466 non-obese (body mass index < 28 kg/m2) and 123 obese ( ≥ 28 kg/m2) men including 138 patients with Type II (non-insulin-dependent) diabetes mellitus.¶Results. Three loci of single nucleotide substitution (G→A at –995, C→T at –759, G→C at –697) and a (GT)n dinucleotide repeat polymorphism at –1,027 were identified. The frequency of –995/–759 and –697 variants was higher in non-obese subjects and that of –995/–759 variants in non-diabetic subjects. In the dinucleotide repeat locus, five alleles were detected including Z containing 17 repeats. The Z-6 allele was more common in non-obese subjects and the Z + 2 allele in obese subjects. Haplotype 3 (Z-6, –995A, –759T, –697C) was associated with leanness (p = 0.02) and the absence of diabetes (p = 0.033) and haplotype 9 (Z + 2, –995G, –759C, –697G) with obesity (p = 0.007). Haplotype 2 (Z-6, –995G, –759C, –697C) tended to be more common in non-obese subjects. A luciferase reporter assay showed that haplotype 2 and haplotype 3 had 1.44- or 2.58-fold higher promoter activities than the most common haplotype 6 (Z, –995G, –759C, –697G).¶Conclusion/interpretation. The haplotypes containing the nucleotide substitutions could be associated with higher transcription levels of the gene and thereby with resistance to obesity and Type II diabetes. Promoter polymorphisms of the 5-HT2C receptor gene may play an important part in genetic predisposition to the disorders. [Diabetologia (2000) 43: 373–376]
- Publication
Diabetologia, 2000, Vol 43, Issue 3, p373
- ISSN
0012-186X
- Publication type
Academic Journal
- DOI
10.1007/s001250050056