Risk of microalbuminuria in relatives of subjects with diabetic nephropathy: a predictive model based on multivariable dimensionality reduction approach

摘要

Abstract. Aim: To evaluate a predictive model of microalbuminuria by using anthro-pometric, clinical and genetic variables in relatives of subjects with diabetic nephropa-thy. Methods: Eligible subjects, aged 18-63 years with body mass index < 35 kg/m2, and first degree relatives of patients with type 2 diabetes and diabetic nephropathy were enrolled in a cross-sectional study. A total of 70 individuals with microalbuminuria were compared with 60 individuals without microalbuminuria. Based on a morning uri-nary sample, microalbuminuria was defined as albumin > 30 < 300 mg/dL. Genotyping of single nucleotide polymorphisms (SNPs) G-174C of IL6 (rs 1800795), G-308A of TNF (rs 1800629), and Pro12Ala of PPARy2 (rsl801282) genes were determined. The multivariable dimensionality reduction anal-ysis was performed using the software mul-tifactor dimensionality reduction package. Results: The multivariable dimensionality reduction analysis showed that obesity and SNP G-308A of TNF gene exhibited main effects with 1.10 and 1.98% of information gain (IG), respectively. The IL6 showed syn-ergy (interaction) with HDL-c (IG 1.27%) and sex (IG 1.02%); also high-sensitivity C-reactive protein and triglycerides levels showed synergy (IG 1.08%). The consis-tency of the cross-validation for this model was 0.6836, with sensitivity and specificity of 0.58 and 0.76 (odds ratio 4.64; 95% CI 4.0 - 10.0, p < 0.0001). Conclusion: Our re-sults indicate that obesity and/or high blood pressure, in synergism with high-sensitivity C-reactive protein and high-density lipopro-tein cholesterol levels, is the main predictive risk factor of diabetic nephropathy in healthy subjects, relatives of patients with type 2 dia-betes and diabetic nephropathy.