Effect of dietary calcium on the gender-specific association between polymorphisms in the PTPRD locus and...

Osteoporosis is the most common bone disease and is characterized by low bone mineral density (BMD) and a high risk of fracture. Despite advances in our understanding of the pathogenesis of osteoporosis, complex gene-environment interactions that influence osteoporosis development remain largely unexplored. In this study, we aimed to identify genetic loci associated with low BMD and to evaluate these genetic variants under individual and environmental factors.

A genome-wide association analysis was conducted using 500,568 single-nucleotide polymorphisms (SNPs) in 8842 individuals aged 40-69 years using clinical, demographic, and dietary data (>260 traits) established by the Korean Genome and Epidemiology Study. The gPLINK program was used to detect SNPs associated with osteoporosis at a genome-wide significance level (P < 1.0 × 10^-05) and conduct a haplotype analysis. Statistical differences between the osteoporosis and control groups in categorical variables (sex and dietary profiles) were assessed based on frequency distributions using the chi-squared test.

Of the seven SNPs that were associated with osteoporosis, both rs10977574 and rs4390000 lay in the PTPRD locus encoding a protein tyrosine phosphatase-receptor type D, which has been implicated in bone metabolism. Haplotype analysis identified two minor alleles, C and G, at the rs10977574 and rs4390000 loci, respectively, forming a linkage disequilibrium block. The subsequent gender-stratified analysis using dietary calcium intake revealed an increased correlation between the CG haplotype and osteoporosis (OR = 2.069) in the low-calcium-intake-female group but not in the high-calcium-intake-female or any male group.

This study revealed novel evidence of the sex-specific association of the CG haplotype in the PTPRD locus with osteoporosis and indicated that the association can be influenced by dietary calcium intake.