Voprosy meditsinskoi khimii (ISSN 0042-8809)

The mutation screening of proopiomelanocortin gene related to human obesity


1. Endocrine Research Centre of RAMN
2. Endocrine Research Centre of RAMN, Scientific Centre of Psychiatric Health of RAMS
3. Institute of Nutrition of RAMS
4. Scientific Centre of Psychiatric Health of RAMS
PubMed Id: 12068494
Year: 2002 vol: 48  issue:1  pages: 120-131
Abstract: Proopiomelanocortin (POMC) is a precursor of ACTH, b- and g-liportopins, a-, b- and g-MSH, b-endorphin. a-, b- and g-MSH are synthesized by hypothalamus neurons, and leptin stimulates their synthesis. These hormones regulate food consumption and energy metabolism by via melanocortin receptors (MC3-R and MC4-R) in hypothalamus. Screening mutations in the coding region of human POMC has been carried out with PCR, SSCP and DNA sequencing and the association study of these mutations and human obesity has been performed. Group of patients with the exogenous obesity (BMI 37,8±6,8 kg/m2) consisted of 228 persons (173 women and 55 men). 145 blood donors (67 women and 78 men) without obesity (BMI Ј25 kg/m2, 23.1±2,2 kg/m2) and 170 women without apparent obesity at the beginning of the study were included in the control group. 8 polymorph sites: insertions; missense and silent mutations have been identified in the coding region of POMC. Among them 1) two heterozygous mutations: the insertion of 6 b.p. (GGGCCC) in codon 176 inducing the insertion of two amino acid residues (Arg-Ala) in POMC and nonsense mutation (G-7316-T) in codon 180 of g-LTH coding region of the same DNA chain were identified in 4 women (5.8%) out of 69 patients with morbid obesity (BMI 40-53 kg/m2). These mutations were not found in control (n=315). 2) The new heterozygous mutation T-7130-C (Phe118Leu) in active site of a-MSH has been identified in POMC gene of a woman suffering with obesity since the early childhood. 3) Mutation A-7341-G (Glu188Gly) seemed to have a protective effect because it was revealed more frequently in control (3.9 %) than in obese patients (0.66%). The results of genetic study of two pedigrees suggested the dominant influence of the first two mutations (1 and 2) on woman obesity.
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Reference: Pankov Yu.A., Yatcishina S.B., Karpova S.K., Chekhranova M.K., Popova Yu.P., Grigorvan O.N., Rogaev E.I., The mutation screening of proopiomelanocortin gene related to human obesity, Voprosy meditsinskoi khimii, 2002, vol: 48(1), 120-131.