Genetic and Environmental Pathways in Type 1 Diabetes Complications

摘要

Genetic factors contribute to risk for developing nephropathy in patients with Type 1 Diabetes (T1D). Cigarette smoking is deleterious to kidney function and is a risk factor for Diabetic-Nephropathy (DN) as well as End Stage Renal Disease (ESRD) in patients with T1D. The proposed study investigates how environmental exposure(s) (e.g., smoking) and genetic variants interact to amplify risk for T1DN and substantially increase incidence of ESRD. The specific aims are: 1) Identify genetic variants conferring risk to T1DN by performing a staged follow-up of our initial Genome-Wide Association Scan (GWAS) results; 2) Ensure that SNPs identified by Aim 1 affect risk of T1DN, as opposed to risk for T1D; 3) Identify genetic variants that interact with smoking status in conferring risk for T1DN; 4) Confirm results obtained during Aims 1-3 using an independent cohort of case and control participants. The relevance of the study to public health is that 16 million people in the US have diabetes with 800,000 new cases diagnosed each year. Diabetic complications threatening vision, kidney, and nerve function affect most diabetic patients. Improved prediction of risk for developing diabetes and diabetic complications among active duty members of the military, their families and retired military personnel will potentially allow focused preventative treatment of at risk individuals, providing significant healthcare savings and improved patient well being.