GENETIC ASSOCIATION BETWEEN MILD HYPERGLYCEMIA AND MICROALBUMINURIA IN GENERAL POPULATION

Abstract

Introduction and Aims: Increased glycemic exposure, even below the diagnostic criteria of diabetes mellitus (DM), is critical in pathogenesis of microvasular complication of diabetes mellitus, but the role of genetic polymorphism in this association remains to be determined. We performed genome-wide association study (GWAS) to find susceptible single-nucleotide polymorphisms (SNPs) associated with both mild hyperglycemia and microalbuminuria in general population.

Methods: We analyzed anthropometric, biochemical, and genetic data from a community-based study (the KoGES). Eligible as cases were all native Koreans without significant medical illness. A total of 5682 participants were classified into control (n = 3153) or prediabetes (n = 2529) according to the ADAGuideline-2015. Microalbuminuria was defined as urine albumin/creatinine ratio (UACR, mg/g Cr) between 30 and 300.

Results: Multiple linear regression analysis showed that there UACR had positive relationship between fasting glucose and glycated hemoglobin levels, but not post-prandial glucose. Subsequent GWAS revealed that a susceptibility locus at the GCK gene (encoding Hexokinase 4) at 17p13 was associated with mild hyperglycemia. Multiple logistic analysis showed that genetic polymorphism at rs2908289 of GCK gene were independently associated with microabuminuria and further adjustment for age, gender, systolic blood pressure, albumin, smoking history, and serum triglyceride level did not attenuate this association.

Conclusions: Our results suggest that genetic polymorphism in the GCK gene is associated with susceptibility to microvascular complication in subject with prediabetes. Further study is needed to explore the details of the physiological and molecular mechanisms underlying this association.