The role of GLP-1 R variants on body weight response after dietary intervention is unclear. Our aim was to evaluate the effect of this polymorphism on cardiovascular risk factors, adipokine levels and weight loss secondary to a high monounsaturated fat vs. a high polyunsaturated fat hypocaloric diets in obese subjects. 391 obese subjects were randomly allocated to one of these two diets for a period of 3 months; diet M (high monounsaturated fat hypocaloric diet) and diet P (high polyunsaturated (PUFAs) fat hypocaloric diet). Two hundred and twelve patients (54.2 %) had the genotype GG (wild group) and 179 (45.8 %) patients had the next genotypes; GA (146 patients, 37.3 %) or AA (33 patients, 8.7 %) (Mutant group). With both diets and in wild-type and mutant-type groups, BMI, weight, fat mass, waist circumference and systolic blood pressure decreased. Anthropometric parameters were higher in non-A-allele carriers than A-allele carriers. With both diets and in both genotypes, leptin, insulin levels and HOMA decreased. With the diet P and in wild genotype, total cholesterol and LDL-cholesterol levels decreased, too. Our data showed a lack of association of rs6923761 GLP-1 R polymorphism with weight loss after a high monounsaturated fat and a high polyunsaturated fat hypocaloric diets. Better anthropometric parameters in obese subjects with the mutant allele (A) of rs6923761 GLP-1 R polymorphism were observed. Insulin levels and HOMA decreased in non-A carriers.
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