Polymorphisms in the Neuropeptide Y Gene and the Risk Of Obesity: Findings from Two Prospective Cohorts

Context: Neuropeptide Y(NPY) increases appetite and food intake in animals. Conflicting evidence has been found for the association between polymorphisms of the NPY gene and obesity in humans. Objective: The objective of the investigation was to study four single-nucleotide polymorphisms(SNPs) in the NPY gene [rs17149106 (G>T), rs16147 (C>T), rs16139 (T>C), rs5574 (C>T)] with body adiposity. Design: The study design included a candidate gene association study from two cohorts. Participants: Two thousand seventy-one women from the Nurses' Health Study and 1268 men from the Health Professionals Follow-Up study participated in the study. Main Outcome Measures: Weight and height were self-reported at baseline and updated every 2 yr to calculate body mass index (BMI). Results: Two SNPs (rs17149106 (G>T) andrs16139 (T>C)), with minor allele frequencies of 4%, were associated with elevated risks of obesity (BMI >= 30 kg/m(2)) in both cohorts. The pooled adjusted odds ratios[95% confidence interval (CI)] were1.72(95% CI 1.20-2.47) and 1.79(95% CI 1.24-2.60), respectively. Haplotype analyses reflected the associations with the individual SNP. TTCC carriers, with the minor allele of both SNPs, had an increased risk of obesity (odds ratio 1.89; 95% CI 1.29-2.75) compared with those carrying the common haplotype GCTT. Carriers of the rs16139 C allele had greater BMI than noncarriers with a pooled mean difference of +/- 0.58 kg/m(2) (95% CI 0.01-1.15) among women and men. Both rs17149106 and rs16139 were associated with weight gain since adolescence/early adulthood but were not associated with abdominal adiposity as measured by waist circumference and waist to hip ratio. Conclusions: NPY gene variants were significantly associated with weight changes from young adulthood to middle age and with risk of obesity. (J Clin Endocrinol Metab 96: E2055-E2062, 2011)