ABSTRACT: OBJECTIVE:To investigate the association between SNP in the BTNL2 gene region and the susceptibility to osteoarthritis of the knee. METHODS:The blood samples of 103 knee osteoarthritis and 134 healthy subjects were collected. Four SNP in the BTNL2 gene region were selected, whole DNA was extracted using the QIAamp blood DNA purification mini reagent, the BTNL2 gene fragment was amplified and sequenced, and the genotype and corresponding frequency were counted. The results were statistically analyzed. RESULTS:The four SNP (rs41521946, rs28362677, rs28362678, rs28362675) in the BTNL2 gene region were analyzed using a chi-square test (mutation heterozygote, homozygous, and normal homozygote), and the genotypes of the four mutation points were found to be statistically significant (P=0.003, 0.013, 0.005, and 0.045, respectively). Among the four SNP, the first three SNP were in Hardy-Weinberg equilibrium, and a multivariate logistic regression analysis was used to correlate them with knee osteoarthritis (P=0.003, 0.013, 0.005, respectively). rs28362675 was not in Hardy-Weinberg equilibrium but was associated with knee osteoarthritis (P=0.045), which might be smaller samples or an ethnicity differential allelic variation. The P values of the statistical analysis of age and height in the baseline data of both groups were less than 0.05. Considering the possible impact on the results, they were used as covariates in the analysis. The SNP of rs41521946 and rs28362677 showed a significant change in their associations with mutations, and the genotype P values of rs41521946 (AC+AA)/CC and rs2836267 (AG+AA)/GG were 0.002, 0.006, respectively. CONCLUSION:Four SNP (rs41521946, rs28362677, rs28362678, rs28362675) in the BTNL2 gene region were significantly associated with knee osteoarthritis, and the target population might be significantly affected by rs28362675.