Human Molecular Genetics Advance Access originally published online on June 15, 2009
Human Molecular Genetics 2009 18(18):3496-3501; doi:10.1093/hmg/ddp280
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Association of variants in the PCSK1 gene with obesity in the EPIC-Norfolk study
1 MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge CB2 0QQ, UK, 2 CNC, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK and 3 Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 0SR, UK
* To whom correspondence should be addressed at: MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. Tel: +44 1223769164; Fax: +44 1223330316; Email: tuomas.kilpelainen{at}mrc-epid.cam.ac.uk
Received April 1, 2009; Revised May 19, 2009; Accepted June 11, 2009
Recently, the rs6232 (N221D) and rs6235 (S690T) SNPs in the PCSK1 gene were associated with obesity in a meta-analysis comprising more than 13 000 individuals of European ancestry. Each additional minor allele of rs6232 or rs6235 was associated with a 1.34- or 1.22-fold increase in the risk of obesity, respectively. So far, only one relatively small study has aimed to replicate these findings, but could not confirm the association of the rs6235 SNP and did not study the rs6232 variant. In the present study, we examined the associations of the rs6232 and rs6235 SNPs with obesity in a population-based cohort consisting of 20 249 individuals of European descent from Norfolk, UK. Logistic regression and generalized linear models were used to test the associations of the risk alleles with obesity and related quantitative traits, respectively. Neither of the SNPs was significantly associated with obesity, BMI or waist circumference under the additive genetic model (P > 0.05). However, we observed an interaction between rs6232 and age on the level of BMI (P = 0.010) and risk of obesity (P = 0.020). The rs6232 SNP was associated with BMI (P = 0.021) and obesity (P = 0.022) in the younger individuals [less than median age (59 years)], but not among the older age group (P = 0.81 and P = 0.68 for BMI and obesity, respectively). In conclusion, our data suggest that the PCSK1 rs6232 and rs6235 SNPs are not major contributors to common obesity in the general population. However, the effect of rs6232 may be age-dependent.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Hardy, A. K. Wills, A. Wong, C. E. Elks, N. J. Wareham, R. J.F. Loos, D. Kuh, and K. K. Ong Life course variations in the associations between FTO and MC4R gene variants and body size Hum. Mol. Genet., November 12, 2009; (2009) ddp504v2. [Abstract] [Full Text] [PDF]
|
|