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J Clin Endocrinol Metab. 2011 Dec;96(12):E2055-62. doi: 10.1210/jc.2011-0195. Epub 2011 Sep 21.

Polymorphisms in the neuropeptide Y gene and the risk of obesity: findings from two prospective cohorts.

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  • 1Epidemiology Branch, Division of Epidemiology, Statistics, and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6100 Executive Boulevard, 7B03, Bethesda, Maryland 20892, USA.



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.


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.


The study design included a candidate gene association study from two cohorts.


Two thousand seventy-one women from the Nurses' Health Study and 1268 men from the Health Professionals Follow-Up study participated in the study.


Weight and height were self-reported at baseline and updated every 2 yr to calculate body mass index (BMI).


Two SNPs (rs17149106 (G>T) and rs16139 (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)] were 1.72 (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.


NPY gene variants were significantly associated with weight changes from young adulthood to middle age and with risk of obesity.

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