A functional haplotype in EIF2AK3, an ER stress sensor, is associated with lower bone mineral density.

ABSTRACT: EIF2AK3 is a type I transmembrane protein that functions as an endoplasmic reticulum (ER) stress sensor to regulate global protein synthesis. Rare mutations in EIF2AK3 cause Wolcott-Rallison syndrome (OMIM 226980), an autosomal recessive disorder characterized by diabetes, epiphyseal dysplasia, osteoporosis, and growth retardation. To investigate the role of common genetic variation in EIF2AK3 as a determinant of bone mineral density (BMD) and osteoporosis, we sequenced all exons and flanking regions, then genotyped six potentially functional single nucleotide polymorphisms (SNPs) in this gene in 997 Amish subjects for association analysis, and attempted replication in 887 Mexican Americans. We found that the minor allele of a nonsynonymous SNP rs13045 had borderline associations with decr

SUBMITTER: Liu J 

PROVIDER: S-EPMC3319695 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature