Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

Abstract

Background: Gut hormones and their receptors are considered important in the control of feeding behavior. The gut hormone peptide-YY (PYY) has anorexic effects via the inhibitory neuropeptide Y2 receptor (Y2R) highly expressed in orexigenic NPY/ AGRP neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus. Design: Genetic case-control association study of single nucleotide polymorphisms (SNPs) in Y2R and PYY. Subjects: Swedish Caucasians comprising 148 lean, 129 overweight/obese and 226 morbidly obese men. Measurements: Genotypes of the common, silent and conserved SNP Y2R 585T4C and the common SNP PYY Arg72Thr, as well as various obesity-related clinical parameters. Results: Obese men had a lower allele and homozygosity frequency of the common allele 585T4C:T which was particularly evident comparing morbidly obese with lean men (P ¼ 0.002), and analyzing dependence between continuous body mass index (BMI) and genotype (P ¼ 0.002). In agreement, systolic blood pressure tended to be lower in those homozygous for allele T, which was not explained by the BMI -genotype dependence. We found no association to obesity for the PYY Arg72Thr polymorphism, which is located nearby the essential carboxy terminal. Conclusion: A common and conserved variant of the PYY and NPY receptor Y2R is less prevalent among obese compared to among lean Swedish men. This suggests that the common Y2R variant is protective against obesity. Our findings further implicate Y2R in food intake regulation.

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

“…However, from our results it was observed that the dominant model (CC vs CT+TT) for SNP rs6857715 was more significant for the obese children (p=0.007), and this model was also found to be more significant in the obese adults (p=0.004). This SNP was not studied in either the British white subjects [36] or the Swedish men [37].…”

“…The study in the Swedish men concentrated on the previously associated NPY2R gene variant 585T>C (rs1047214) and the PYY gene Arg72Thr variant (rs1058046). No association was found for the PYY gene variant; however, the common TT genotype of the 585T>C variant was found to be protective against obesity in the Swedish men (p=0.002) [37]. Less is known about rare variants in these appetite-regulating genes and their role in predisposition to obesity.…”

“…Three previous published studies have focused on both the PYY and NPY2R genes [35][36][37], while two further studies have focused on PYY variants alone in association with type 2 diabetes [38,39] and overweight [39]. In British white subjects two common single nucleotide polymorphisms (SNPs) in exon 2 (585T>C and 936T>C) of the NPY2R gene were in strong linkage disequilibrium (LD).…”

SNP analyses of postprandial responses in (an)orexigenic hormones and feelings of hunger reveal long-term physiological adaptations to facilitate homeostasis

“…As the 585T4C SNP is a silent transition, this SNP is likely to be in LD with a functional variant in the NPY2R locus. 46 To summarize, the 223Arg-encoding allele may increase food intake by decreasing leptin sensitivity, it may decrease food intake by increasing plasma leptin levels and by increasing the postprandial response in plasma ghrelin levels, and it may either increase or decrease food intake by influencing the postprandial response in feelings of hunger depending on the 585T4C SNP (NPY2R). The phenotypes determined in the present study were not independent and two of the SNPs evaluated were in LD.…”

Association between BBS6/MKKS gene polymorphisms, obesity and metabolic syndrome in the Greek population

“…The fact that the T allele is less prevalent among obese compared to non-obese individuals, suggests that the synonymous 1129C4T variation may play a protective role against obesity. A protective role has been attributed to other SNPs as well, for example, the 585T4C (I195I) SNP of the neuropeptide Y2 receptor gene 31 or the 307A4G (V103I) variant of the melanocortin-4 receptor gene. 32 Polymorphism 1129C4T is not in LD with the other six SNPs; however, it may express its own effect on the phenotype or it may be in LD with other functional variants.…”