ISSN:
1432-0428
Keywords:
Keywords Serotonin, 5-HT2C receptor, promoter, polymorphism, obesity.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s001250050056
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