COLGALT2 Polymorphisms are Associated with Osteoarthritis Risk and Clinical Severity in a Chinese Population

Osteoarthritis (OA) is a highly heritable joint disease. Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) within the collagen beta(1-O) galactosyltransferase 2 (COLGALT2) gene region, notably rs11583641 and rs1046934, to OA risk. Their roles in Chinese populations, clinical phenotypes, and gene expression remains unclear.

This case-control study, 230 primary OA patients and 230 matched healthy controls were genotyped for rs11583641 and rs1046934 using the TaqMan assay. OA was diagnosed per American College of Rheumatology (ACR) and Kellgren-Lawrence (K-L) grading. Logistic regression assessed independent associations with OA. COLGALT2 expression in peripheral blood mononuclear cells (PBMC) was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Allele and genotype distributions of rs11583641 and rs1046934 differed significantly between case and control groups (P<0.025). Multivariate regression adjusted for age, sex, and BMI showed that rs11583641 and rs1046934 remained associated with OA susceptibility (P<0.05). Cross-sectional subgroup analyses showed that rs11583641 polymorphism significantly associated with disease duration (P<0.025) and imaging severity (P<0.025). COLGALT2 expression was higher in OA patients than controls (P< 0.05). Its expression associated with risk genotypes, with the same trend at both loci: highest in rs11583641 CC and rs1046934 AA carriers, followed by CT and AC carriers, and lowest in TT and CC carriers.

This study provides additional evidence supporting the association of COLGALT2 SNPs with OA susceptibility in a Chinese population. Cross-sectional subgroup analyses suggested that rs11583641 may be associated with severity-related clinical phenotypes. Increased PBMC COLGALT2 expression and its association with risk genotypes offer preliminary correlative evidence warranting further investigation, as these findings may be influenced by systemic inflammation, leukocyte composition, or other confounding factors. Further longitudinal and functional studies are required to clarify its clinical and biological significance. These findings provide additional insights into the genetic and molecular heterogeneity of OA.