Genome-wide association study identifies variants in PMS1 associated with serum ferritin in a Chinese population

PLoS One. 2014 Aug 27;9(8):e105844. doi: 10.1371/journal.pone.0105844. eCollection 2014.

Abstract

Only a small proportion of genetic variation in serum ferritin has been explained by variant genetic studies, and genome-wide association study (GWAS) for serum ferritin has not been investigated widely in Chinese population. We aimed at exploring the novel genetic susceptibility to serum ferritin, and performed this two stage GWAS in a healthy Chinese population of 3,495 men aged 20-69 y, including 1,999 unrelated subjects in the first stage and 1,496 independent individuals in the second stage. Serum ferritin was measured with electrochemiluminescence immunoassay, and DNA samples were collected for genotyping. A total of 1,940,243 SNPs were tested by using multivariate linear regression analysis. After adjusting for population stratification, age and BMI, the rs5742933 located in the 5'UTR region of PMS1 gene on chromosome 2 was the most significantly associated with ferritin concentrations (P-combined = 2.329×10(-10)) (β = -0.11, 95% CI: -0.14, -0.07). Moreover, this marker was about 200 kb away from the candidate gene SLC40A1 which is responsible for iron export. PMS1 gene was the novel genetic susceptibility to serum ferritin in Chinese males and its relation to SLC40A1 needs further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Adult
  • Age Factors
  • Aged
  • Asian People
  • Biomarkers / metabolism
  • Body Mass Index
  • Cation Transport Proteins / genetics
  • Chromosomes, Human, Pair 2 / chemistry
  • Female
  • Ferritins / blood
  • Ferritins / genetics*
  • Gene Expression
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • MutL Proteins
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*

Substances

  • 5' Untranslated Regions
  • Biomarkers
  • Cation Transport Proteins
  • Neoplasm Proteins
  • PMS1 protein, human
  • metal transporting protein 1
  • Ferritins
  • MutL Proteins

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (81260130, 81060234, 30945204, 30360124, 30260110), Key Program and University Talents Highland Innovation Team of Guangxi (2012012D003, GJR201147-09), Chairman Science and Technology Fund and Tackle Program of Guangxi (1116-03, GKG1298003-07-01), Guangxi Science Fund for Distinguished Young Scholars (2012GXNSFFA060009), Guangxi Natural Science Foundation (2012GXNSFDA053016), Guangxi Graduate Education Innovation Program (2010105981002M175 and 2011105981002M202) and Guangxi Provincial Department of Finance and Education (2009GJCJ150). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.