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 (> or = 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.
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 (> or = 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.
Authors: Y Zhang; E M Smith; T M Baye; J V Eckert; L J Abraham; E K Moses; A H Kissebah; L J Martin; M Olivier Journal: Physiol Genomics Date: 2010-04-13 Impact factor: 3.107
Authors: Sofia I I Kring; Thomas Werge; Claus Holst; Søren Toubro; Arne Astrup; Torben Hansen; Oluf Pedersen; Thorkild I A Sørensen Journal: PLoS One Date: 2009-08-19 Impact factor: 3.240