Andersson has described a detailed calculation method of additive interaction, an SAS programme, including toward instructions for how to adjust the programme for use in SPSS, and an Excel calculator available from EpiNET which we used to estimate the three indicators of interaction and 95% CI. The method follows the approach proposed by Lundberg et al. to calculate three measures of additive interactions relative excess risk due to interac tion, attributable proportion and synergy index, and a method suggested by Hosmer and 4. 7 fold higher when both risk factors were present, suggesting an antagonistic interaction between the variant allele of this polymorph ism and being overweight. Inhibitors,Modulators,Libraries Similar stratified analysis for hip OA is presented in Table 3.

For example, for SNP rs1800468, the risk for hip OA was significantly Inhibitors,Modulators,Libraries elevated in overweight individuals only but there was no sig nificant association with genotype 1222 only. However, there was a 2 fold risk for hip OA when both risk factors were pre sent, suggesting a synergistic interaction between the var iant allele of this polymorphism and being overweight. Interaction term in the models Table 4 shows a summary of significant results from the analysis of interaction between TGFb1 polymorphisms and Inhibitors,Modulators,Libraries BMI in OA. For knee OA, a significant antagonistic interaction on both Inhibitors,Modulators,Libraries the multiplicative and additive scale was observed for SNP rs2278422. Assuming a multiplicative scale, the OR for interaction was 0. 47 whilst under an additive scale, the AP was 0.

61, indicating that both factors acted antagonistically in relation to risk of knee OA, so that the AP to knee OA was 61% lower than expected from the addition of separate effects of genotype 1222 and being overweight. Additive interaction was also observed between SNP rs11466321 and being overweight but this effect became Inhibitors,Modulators,Libraries null after adjusting for potential confounders. Furthermore, no statistically significant mul tiplicative interaction was found for this SNP. For hip OA, an additive interaction was observed between SNP rs1800468 and being overweight. Both fac tors acted synergistically to increase the risk of hip OA, so that among overweight persons carrying the variant allele, 42% of hip OA risk was attributable to the action of both exposures as compared with the contri bution of each of the two risk factors added to each other.

A significant multiplicative interaction for this SNP was also found. Discussion This is the selleckchem first study to examine possible interactions between increased BMI and TGFb1 gene polymorphisms for knee and hip OA. We found significant additive and multiplicative interaction between being overweight and the variant allele of TGFb1 SNP rs2278422 in knee OA but in hip OA these interactions were indicated by TGFb1 SNP rs1800468.