The rs3740199 G/C polymorphism was found to be associated with increased KOA risk in men (e.g., CG versus GG: OR = 1.44, 95% CI = 1.02-2.04, <i>P</i> = 0.040), but not in the overall analysis and in analyses of other subgroups.
Based on the findings of our study, there was a modest but statistically significant association between rs1871054 and risk of KOA in Asian population, while other polymorphisms (rs3740199, rs1044122, or rs1278279) in ADAM12 were not associated with KOA in any population.
The rs3740199 polymorphism of the ADAM12 gene can potentially be used to determine genetically high-risk subgroup of knee osteoarthritis and to better understand the pathogenesis of knee osteoarthritis.
Two thousand four hundred and sixty-two subjects aged 50 years and older were assessed for OA at the knee, were genotyped with two SNPs (GDF5; rs143383 and ADAM12; rs3740199).
We found that the rs1871054 was significantly associated with the risk of knee OA (allele model OR 1.72, 95% CI 1.43-2.07, P < 0.001; additive model: OR 2.06, 95% CI 1.19-3.56, P = 0.010; dominant model: OR 2.45, 95% CI 1.85-3.25, P < 0.001; recessive model: OR 1.54, 95% CI 1.13-2.10, P = 0.007). rs1044122 was significantly associated with knee OA susceptibility in recessive model (OR 1.45, 95% CI 1.03-2.04, P = 0.031).
In summary, we have identified that the rs1871054 variant within the ADAM12 gene is a risk factor for increased osteoarthritis susceptibility and severity.
In conclusion, our data demonstrated the ADAM12 rs1871054 variant was found to be significantly associated with increased OA susceptibility in a Chinese Han population.
Based on the findings of our study, there was a modest but statistically significant association between rs1871054 and risk of KOA in Asian population, while other polymorphisms (rs3740199, rs1044122, or rs1278279) in ADAM12 were not associated with KOA in any population.
Overall, five different studies, totaling 2,353 cases and 3,668 controls, were retrieved on the basis of the search criteria for KOA susceptibility related to four polymorphisms (rs3740199, rs1278279, rs1871054, and rs1044122) in the <i>ADAM12</i> gene.
In the stratified analysis by gender, significant association was identified with the risk of knee OA for rs3740199 in men in allele model (OR 2.41, 95% CI 1.51-3.84, P < 0.001), dominant model (OR 2.68, 95% CI 1.17-6.14, P = 0.02) and recessive model (OR 3.51, 95% CI 1.68-7.36, P = 0.001), but not for additive model (OR 1.30, 95% CI 0.81-2.08, P = 0.28).
The rs3740199 in ADAM12 was associated with knee OA susceptibility in Thai male patients, and individuals with the CC genotype carried the highest risk when compared with the GG and GC genotypes.