Characteristics of subjects in study
Detailed information of all individuals in study is shown in Table 1. The average ages of the patient and control groups were 61.39 and 61.03 years old, respectively and mean BMIs were 24.61 and 24.58 kg/m2, respectively. There were no significant differences between the groups in regard to age, BMI, or sex, and the distributions of smokers and drinkers were equal group. Table 1 lists the relevant indexes, including affected leg, CRP, ESR, VAS, Lequensene’s index, and the K-L grade.
Relationship between the IL-6 rs12700386 polymorphism and OA risk
The allele and genotype distribution of IL-6 rs12700386 polymorphism is shown in Table 2. The HWE test found that there was no obvious deviation in genotypic frequency among the controls, indicating that the subjects in this study are representative of the local population. The IL-6 rs12700386 polymorphism led to an obvious increase in the risk of OA risk in dominant, homozygous, and allelic models. A logistic regression analyses showed that the CC genotype significantly increased the risk of OA (CC vs. GG: OR and 95% CI, 2.01 (1.04, 3.89), P=0.045). (Table 2). Analysis of the allelic model revealed that the C allele was associated with a higher risk of OA (C vs. G: 1.38 (1.08, 1.75), P=0.010) (Table 2). This significant association was also observed in the dominant models. Stratified analyses of age, smoking, drinking status, and BMI revealed that there was a significantly higher risk of OA in drinkers, smokers, those over 55 years old, and with a BMI above 25 kg/m2. (Table 3). The rs12700386 polymorphism however, did not affect the risk of OA in regard to the abovementioned indexes (Table 5).
Based on the RT-PCR analysis, higher IL-6 expression was seen in the CC genotype compared to the GG genotype (P < 0.001) (Figure 1).
Association between IL-6 rs12700386 polymorphism and serum IL-6 levels
Data indicated that the average IL-6 serum levels were significantly higher in OA patients (P < 0.001, Supplemental Figure 1 a) and that genotype CC patients had higher IL-6 serum levels compared to genotype GG patients (P < 0.05, Supplemental Figure 1 b). However, this polymorphism was not associated with alteration in IL-6 serum levels in the control subjects (Supplemental Figure 1 c).
The OR and 95% CI specific to two combining exposure models (IL-6 gene variants and smoking or drinking) were calculated (Table 4). With regards to the rs12700386 polymorphism, the GG genotype had a more obvious effect on the risk of OA than the CC genotype. While smoking was shown to have no impact on the risk of OA, smokers carrying the CC genotype were more likely to suffer from OA compared to non-smokers carrying the GG genotype (OR, 2.86, 95%CI, 1.25–6.56; P = 0.015). This indicated that there may be an interaction between the CC genotype and smoking. No interaction was seen between the GC genotype and smoking in terms of OA risk. A combined effect on OA risk was seen with the CC genotype of rs12700386 polymorphism and drinking, suggesting that there was an interaction between the CC genotype and drinking. There was no interaction between the GC genotype and drinking in terms of OA risk.