The association of AKNA gene polymorphisms with knee osteoarthritis suggests the relevance of this immune response regulator in the disease genetic susceptibility

Recent studies have identified AKNA as a potential susceptibility gene for several inflammatory diseases. Here, we aimed to assess the potential association of AKNA polymorphisms with knee osteoarthritis (KOA) susceptibility in a Mexican population, following STREGA recommendations. From a DNA bank of 181 KOA patients and 140 healthy controls, two AKNA SNPs were genotyped using TaqMan probes. The association between KOA susceptibility and AKNA polymorphisms genotypes was evaluated by multivariated logistic regression analysis. Information regarding patients’ inflammatory biomarkers levels was obtained and their association with AKNA polymorphisms genotypes was assessed by lineal regression. We found a positive association with the recessive inheritance model of both AKNA polymorphisms (A/A genotype for both) and KOA susceptibility adjusting by age, body mass index (BMI), gender and place of birth (OR = 2.48, 95% CI 1.09–5.65 for rs10817595 polymorphism; and OR = 4.96; 95% CI 2.421–10.2 for rs3748176 polymorphism). Additionally these associations were also seen after stratifying patients by KOA severity and age. Furthermore the total leukocyte count was positively associated with rs10817595 AKNA polymorphism (β = 1.39; 95% CI 0.44–2.34) adjusting by age, BMI, gender, place of birth and disease severity. We suggest that regulatory and coding polymorphisms of the inflammatory modulator gene AKNA can influence the development of KOA. Further structural and functional studies might reveal the role of AKNA in OA and other rheumatic diseases.