Modeling the risk of osteopenia and osteoporosis in postmenopausal women with type 2 diabetes on the sets of clinical and immunogenetic parameters

Abstract

Background: Osteoporosis and type 2 diabetes are common comorbidities in postmenopausal women. The value of clinical and immunogenetic risk factors for osteopenia and osteoporosis risk assessment in diabetic patients still needs to be clarified. Aims: to construct the models for assessing the risk of osteopenia and osteoporosis in postmenopausal women with type 2 diabetes on the basis of clinical and immunogenetic parameters. Materials and methods: We studied 197 Caucasian diabetic women, from 50 to 70 years of age. An examination of BMD in the spine, proximal femur and forearm was performed by DEXA. Thirteen polymorphisms in the promoters of TNF A: −238 A/G (rs361525), −308 A/G (rsl800629) and −863 C/A (rsl800630), ILIB: −31 C/T (rsl 143627), IL4: −590 C/T (rs2243250), IL6: −174 C/G (rsl800795), ILIO: −592 C/A (rsl800872) and −1082 A/G (rsl800896), VEGFA: −2578 C/A (rs699947) and +936 C/T (rs3025039), MMP2: −1306 C/T (rs243865), MMP5.· −1171 5A/6A (rs3025058) and MMP9: −1562 C/T (rs3918242), were investigated. Results: Seventy-three women had normal BMD, in 90 ones we revealed osteopenia, and 34 women had osteoporosis. Age, BMI and smoking were strongest predictors of BMD in multivariate regression analysis (p<0.0001, p=0.003 and p=0.01, respectively). In the additive model, C allele and CC genotype in MMP9 −1562 position were associated with low BMD (OR 2.16, p=0.0007 and OR 2.02, p=0.0008, respectively). Association of the polymorphism with BMD remained significant after adjustment for clinical risk factors (p<0.001). Twelve combinations of genotypes associated positively with low BMD were revealed by bioinformatic analysis (all p<0.005). The CC genotype in position −1562 of MMP9, CC genotype in position −863 of TNF A, GG genotype in position −308 of TNFA, and AA genotype in position −1082 of ILIO were the most prevalent variants in these combinations. Conclusions: The combinations of clinical and immunogenetic determinants could be used for assessment of individual susceptibility to osteopenia and osteoporosis in postmenopausal type 2 diabetic women.