caa a22 4500 475771974 CHVBK 20180406123620.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s001250050056 doi (NATIONALLICENCE)springer-10.1007/s001250050056 Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and their association with obesity and Type II diabetes [Elektronische Daten] [X. Yuan, K. Yamada, S. Ishiyama-Shigemoto, W. Koyama, K. Nonaka] 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] Springer-Verlag Berlin Heidelberg, 2000 Keywords Serotonin, 5-HT2C receptor, promoter, polymorphism, obesity nationallicence Yuan X. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, JP aut Yamada K. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, JP aut Ishiyama-Shigemoto S. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, JP aut Koyama W. Kumamoto Red Cross Health Care Centre, Kumamoto, Japan, JP aut Nonaka K. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, JP aut https://doi.org/10.1007/s001250050056 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050056 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yuan X. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, JP aut NATIONALLICENCE 700 1- Yamada K. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, JP aut NATIONALLICENCE 700 1- Ishiyama-Shigemoto S. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, JP aut NATIONALLICENCE 700 1- Koyama W. Kumamoto Red Cross Health Care Centre, Kumamoto, Japan, JP aut NATIONALLICENCE 700 1- Nonaka K. Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, JP aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer