Background: Osteoarthritis (OA) is a complex degenerative joint disease that is associated with both genetic and environmental factors. The AKNA gene, located at 9q32, has recently been identified as being associated with knee osteoarthritis (KOA) in the Mexican population. Our aim was to investigate the relationship of common variants in this gene with the risk of KOA in a large Han Chinese population. Methods: A total of 2,500 Han Chinese subjects were recruited, consisting of 824 KOA patients and 1,676 controls. Eight tag single nucleotide polymorphisms (SNPs) located within the ANKA gene were selected for genotyping. Single marker-based association analyses were conducted using multiple modes of inheritance, including genotypic, allelic, dominant, and recessive. Haplotype-based association analyses were also performed. Plink was utilized for genetic association analyses. In addition, we examined the GTEx database to test the expression quantitative loci effects of the significant SNPs within the AKNA gene. Results: Among these eight SNPs evaluated we identified one, rs10817595, as being significantly associated with the risk of KOA. Compared to the CC genotype at this locus, the odds ratio (95% confidence interval) for KOA with the AA genotype was 1.58 (1.23-2.01)-fold greater. A linkage disequilibrium block that included this SNP was also determined to be significantly associated with the risk of KOA (χ2 = 25.08, p = 3.58 × 10-6). In general, the minor allele A of SNP rs10817595 was associated with an increased risk of KOA. Conclusion: This study is the first to present evidence for a potential link between the risk of KOA and an AKNA gene polymorphism among persons with a Han Chinese ancestry. Future functional analyses based on animal models and sequencing-based population studies are needed to elucidate the biological plausibility and genetic architecture of AKNA for KOA susceptibility.
Keywords: AKNA gene; genetic association; knee osteoarthritis susceptibility; single nucleotide polymorphisms.