Association of single-nucleotide polymorphisms in HLA class II/III region with knee osteoarthritis
2010
Summary Objective A genome-wide association study and a replication using Japanese, Spanish and Greek Caucasian populations have recently indicated two single-nucleotide polymorphisms (SNPs) (rs7775228 and rs10947262) associated with knee Osteoarthritis (OA) susceptibility. We have further evaluated the association in knee OA subjects from Han Chinese and Australian Caucasian origin. Methods Two independent case-control association studies were performed using Han Chinese and Australian Caucasian populations. The two SNPs were genotyped in patients who had primary symptomatic knee OA with radiographic confirmation and/or received total knee replacement surgery as well as in matched controls. They were subjected to statistic analyses. Results A total of 991 OA patients and 1536 controls were genotyped. No significant difference was detected in genotype or allele frequencies of the two SNPs between knee OA and control groups in the two populations (all P >0.05). The association was also negative even after stratification by sex, body mass index (BMI) and Kellgren/Lawrence scores. The significant heterogeneity was detected between Chinese and Japanese (both P P >0.05). The result of meta-analysis showed significant association between knee OA and rs10947262 in total subjects [summary OR=1.26, 95%confidence intervals (CI)=1.07–1.27, P =3×10 −8 ] and in Caucasian samples (summary OR=1.28, 95%CI=1.04–1.57, P =0.02). Conclusion We demonstrated no association between the two SNPs in human leukocyte antigen (HLA) class II/III region and knee OA in Han Chinese population. A significant association was detected between SNP rs10947262 and knee OA in Caucasian subjects. Further replication studies are required to identify the impact of controversial association.
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