Abstract
Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR) = 1.07 (95%CI 0.94 -1.21; p = 0.28). For rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r2 = 0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r2<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.
Highlights
Osteoarthritis (OA) is the most common form of arthritis and the leading cause of physical disability among the elderly in industrialized nations with severely impaired quality of life due to pain and loss of joint functioning [1]
A number of studies have been carried out to determine the genetic determinants of knee OA and a large scale Japanese genome-wide association scan (GWAS) has identified two single nucleotide polymorphisms (SNPs) mapping to the human leukocyte antigen (HLA) gene region to be strongly associated with knee OA [4]
The overall odds ratio (OR) for the risk allele in Caucasians is 0.94 (95%CI 0.81-1.09; p = 0.42; I2 = 26%), using a randomeffects model due to the value of heterogeneity being higher than 25%
Summary
Osteoarthritis (OA) is the most common form of arthritis and the leading cause of physical disability among the elderly in industrialized nations with severely impaired quality of life due to pain and loss of joint functioning [1]. A number of studies have been carried out to determine the genetic determinants of knee OA and a large scale Japanese genome-wide association scan (GWAS) has identified two single nucleotide polymorphisms (SNPs) mapping to the human leukocyte antigen (HLA) gene region to be strongly associated with knee OA [4]. One of the markers identified, rs7775228, mapped to the HLA class II gene DQB1 and reached genomewide significant in Japanese samples (OR = 1.34 95% CI 1.21–1.49 p = 2.4361028) but showed no evidence of association in combined European populations used for replication in the same study (OR = 0.93 95%CI 0.76–1.13). In the Caucasian samples in that study this marker appeared to be associated in the same direction (OR = 1.29 95%CI 1.03–1.61 p = 0.025) and combining both Japanese and Caucasian data rs10947262 achieved genomewide significance (defined as p#561028) [5] overall. A subsequent study by Shi and co-workers tested the same two SNPs in a Chinese case-control study and an Australian case-control study but failed to find a significant association for these SNPs in either group [6]
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