Association Between ALDH1A2 And Susceptibility To Knee Osteoarthritis

Objective A recent genome-wide association study reported significant associations of genetic variants within the ALDH1A2 gene with osteoarthritis(OA)of the hand in European populations.However,these findings have not been well generalized to other joints,or to other populations.To verify this hypothesis,we conducted a population-based case-control study to investigate ALDH1A2 gene with knee OA in China.Methods We performed a two-stage population-based casecontrol study to evaluate whether the ALDH1A2 gene was associated with knee OA in a Chinese population from a community-based study of knee OA in Harbin,a city of Heilongjiang Province,China.In this study,eligible subjects aged 40 and over were enrolled.A questionnaire was designed to collect information from participants regarding general information.All study subjects underwent a physical examination,including anthropometric measurements and radiographic examination.Peripheral blood was collected from each subject only after obtaining sighed information consent.Knee OA case group were identified as those fulfilling the criteria for both clinical and symptom and radiographic findings.While,the healthy control subjects recruited from the same survey,which had no signs or symptoms of arthritis or joint disease.Genotyping was performed using the Sequenom MassARRAY iPLEX platform.Odds ratios(ORs)and their 95% confidence intervals(CI)were calculated by using logistic regression analyses to evaluate the association between SNPs and OA risk.Crossover study was used to analyze the interactions of rs4238326 and environmental factors on OA risk.Results A two-stage population-based case-control study included 196 non-post traumatic knee OA cases and 442 controls in the first stage and independent 143 non-post traumatic knee OA cases and 238 controls in the second stage in a Chinese population.In the first stage,the single nucleotide polymorphism(SNP)rs4238326 was found to be potentially associated with knee OA risk(additive model: odds ratio [OR]=0.70;95% CI=0.49-1.01;P=0.055,which was further confirmed in the second stage with similar effect(additive model: OR=0.60;95%CI=0.38-0.95;P=0.029).After combining the two stages,we found that the variant C allele of rs4238326 was probably associated with decreased risk of knee OA(additive model: OR=0.65;95%CI=0.49-0.86;P=0.003).Furthermore,interaction analyses showed that rs4238326 interacted multiplicatively with age to contribute to knee OA risk(interaction P=0.041).Conclusion These findings indicate that the SNP rs4238326 in ALDH1A2 gene may potentially modify individual susceptibility to knee OA in the Northern Chinese population.Furthermore,rs4238326 interacted multiplicatively with age contribute to OA risk.