Melanocortin-4 receptor gene polymorphism (rs12970134) influences glucose metabolism, leptin and GH levels in women
Olga Bradnova, Marketa Vankova, Petra Lukasova, Josef Vcelak, Hana Kvasnickova & Bela Bendlova
Melanocortin-4 receptor (MC4R) gene is expressed in the brain and has been implicated in mediating most of the effects of melanocortin on food intake and energy expenditure. Common variants of MC4R gene are associated with fat mass, weight, risk of obesity and insulin resistance in several populations.
We investigated if rs12970134 A/G is associated with obesity and studied its possible metabolic effects.
Polymorphism was assesed by ABI TaqMan SNP Genotyping Assay in 842 non-diabetic women: 120 lean (BMI<20 kg/m2), 405 normal weight (BMI 2024.9 kg/m2), 172 overweight (BMI 2529.9 kg/m2) and 145 obese women (BMI>30 kg/m2). All women were detailed anthropometrically and biochemically characterized. The protocol was approved by the Ethical Committee. For statistical analyses the MannWhitney test and χ-square test were used (NCSS 2004).
The allelic frequencies did not differ among groups (minor A allele: lean 23.3%; normal 28%; overweight 21.8%; obese 23.8%) which correspond to the other European populations. Genotypes were in HardyWeinberg equilibrium. Polymorphism was not associated with obesity in our study cohort. Carriers of the minor A allele (AA+AG) versus non-carriers (GG) had significantly lower levels of the fasting glucose (P<0.01), C-peptide (P<0.01), insulin (P<0.01) and better insulin sensitivity (QUICKI; P<0.001). Carriers of A allele had also higher leptin (P<0.05) and GH levels (P<0.01).
In conclusion, we did not confirm the association of rs12970134 of MC4R gene with obesity. However, A allele carrier ship was associated with better glucose metabolism and higher leptin and GH levels. Further study of hypothalamic relations among MC4R leptin GH is needed.
Supported by the grant IGA MHCR NS/10209-3/2009.