Multiple osteoporosis susceptibility genes on chromosome 1p36 in Chinese

Abstract

Introduction: Chromosome 1p36 is a region that has previously shown good evidence of linkage to bone mineral density (BMD) in multiple studies, but the genes that are responsible for the linkage signals are unknown. Materials and methods: We performed a gene-wide and tag SNP-based association study of four positional and functional candidate genes (TNFRSF1B, PLOD, CNR2, and MTHFR) at 1p36 in 1, 243 case-control Chinese subjects. Twenty-three tag SNPs were selected and genotyped using the high-throughput Sequenom genotyping platform. Binary logistic regression analyses were performed to test for genotype associations between each SNP and BMD. Allelic and haplotype association analyses were conducted by Haploview. Gene-gene interactions were investigated using multifactor dimensionality reduction method. Results: The PLOD rs7529452 (C385T; F98F) and MTHFR rs1801133 (C677T; A429E) showed significant genotypic/allelic associations with BMDs at all sites measured (P = 0.08-0.001), and a promising two-locus gene-gene interaction for femoral neck BMD. The CNR2 rs2501431 (A592G; G155G) showed nominally significant allelic associations with trochanter and hip BMD. The TNFRSF1B rs976881 showed genotypic associations with BMDs (P = 0.08-0.04). Conclusions: Our results suggest that multiple genes at 1p36, individually or in different combinations, contribute to osteoporosis susceptibility in Chinese. © 2009 Elsevier Inc. All rights reserved.