Endocrine Abstracts

Agouti related protein (AGRP) as a endogenous antagonist of melanocortin 4 receptor plays an important role in regulation of food intake and energy balance being one of the most potent orexigenic factors. We have determined complete sequence of AGRP gene and upstream promoter region in 100 patients with severe obesity (BMI>35). Three previously described polymorphisms were identified: silent mutation G538A in second exon, non-synonymous mutation G772A (rs5030980) and C662T located in second intron. Association of C662T mutation with obesity this far has not been studied. We further screened this SNP in the cohort of 1173 patients from Latvian Genome database. Carriers of C662T polymorphism had significantly higher BMI when analyzed in all subjects (P=0.017) and in men separately (P=0.028). Mean BMI levels were adjusted for other non-genetic factors including age, status of type 2 diabetes cardiovascular disease and other diseases. After adjustment BMI levels remained significantly higher in men carriers of C662T polymorphism (P=0.035): mean BMI value (with 95% confidence interval) was 29.768 (26.738–33.572) for CT genotype compared with 26.816 (26.432–27.208) for CC genotype. The association of C662T with higher BMI in women was not significant (P=0.051). The present study presents for the first time the association of AGRP polymorphism C662T with obesity in men. The possible functional effects of polymorphism are unclear and may involve splicing defects. Present study has been approved by Latvian Central Committee of Medical Ethics.