Association of PCSK1 rs6234 with Obesity and Related Traits in a Chinese Han Population

Qibin Qi,Hongyu Wu,Huaixing Li,Zhijie Yu,Frank B. Hu,Chen Liu,Xu Lin,Ruth J. F. Loos,Cuilin Zhang

doi:10.1371/journal.pone.0010590

Abstract

BackgroundCommon variants in PCSK1 have been reported to be associated with obesity in populations of European origin. We aimed to replicate this association in Chinese.Methodology/Principal FindingsTwo PCSK1 variants rs6234 and rs6235 (in strong LD with each other, r2 = 0.98) were genotyped in a population-based cohort of 3,210 Chinese Hans. The rs6234 was used for further association analyses with obesity and related traits. We found no significant association of rs6234 with obesity, overweight, BMI, waist circumference, or body fat percentage (P>0.05) in all participants. However, the rs6234 G-allele showed a significant association with increased risk of combined phenotype of obesity and overweight (OR 1.21[1.03–1.43], P = 0.0193) and a trend toward association with obesity (OR 1.25[0.98–1.61], P = 0.08) in men, but not in women (P≥0.29). Consistently, the rs6234 G-allele showed significant association with increased BMI (P = 0.0043), waist circumference (P = 0.008) and body fat percentage (P = 0.0131) only in men, not in women (P≥0.24). Interestingly, the rs6234 G-allele was significantly associated with increased HOMA-B (P = 0.0059) and decreased HOMA-S (P = 0.0349) in all participants.Conclusion/SignificanceIn this study, we found modest evidence for association of the PCSK1 rs6234 with BMI and overweight in men only but not in women, which suggested that PCSK1 rs6234 might not be an important contributor to obesity in Chinese Hans. However, further studies with larger sample sizes are needed to draw a firm conclusion.

Highlights

The PCSK1 gene encodes prohormone convertase 1/3 that converts inactive prohormones into biologically active peptide hormones
We found no significant association between PCSK1 rs6234 risk G-allele and obesity or overweight among all participants (P$0.10) (Table 2)
The PCSK1 rs6234 G-allele showed a significant association with increased risk of combined phenotype of obesity and overweight (P for Single nucleotide polymorphism (SNP)-gender interaction = 0.11) and a trend toward association with increased obesity risk (P for SNP-gender interaction = 0.0458) in men, but not in women (P$0.29) in the gender-stratified analyses (Table 2)

Summary

Introduction

The PCSK1 (prohormone convertase 1/3) gene encodes prohormone convertase 1/3 that converts inactive prohormones (including proinsulin, proglucagon and proopiomelanocortin) into biologically active peptide hormones. A subsequent study in 3,885 non-diabetic Swedes failed to confirm the association between the PCSK1 rs6235 and obesity [6]. Another recent study in 20,249 individuals of European descents from Norfolk, UK, failed to replicate the association of the PCSK1 rs6235 with obesity and related traits, and only found a suggestive evidence for association of the PCSK1 rs6232 with obesity and BMI in younger individuals (age ,59 yrs) but not in older age group [7]. We aimed to examine whether the previously reported association of the PCSK1 genetic variants with obesity and related traits could be replicated in a population-based cohort of Chinese Hans including 3,210 unrelated individuals from Beijing and Shanghai.

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Conclusion