Association of prediabetes-associated single nucleotide polymorphisms with microalbuminuria.
Increased glycemic exposure, even below the diagnostic criteria for diabetes mellitus, is crucial in the pathogenesis of diabetic microvascular complications represented by microalbuminuria. Nonetheless, there is limited evidence regarding which single nucleotide polymorphisms (SNPs) are associated with prediabetes and whether genetic predisposition to prediabetes is related to microalbuminuria, especially in the general population. Our objective was to answer these questions. We conducted a genomewide association study (GWAS) separately on two population-based cohorts, Ansung and Ansan, in the Korean Genome and Epidemiology Study (KoGES). The initial GWAS was carried out on the Ansung cohort, followed by a replication study on the Ansan cohort. A total of 5682 native Korean participants without a significant medical illness were classified into either control group (n = 3153) or prediabetic group (n = 2529). In the GWAS, we identified two susceptibility loci associated with prediabetes, one at 17p15.3-p15.1 in the GCK gene and another at 7p15.1 in YKT6. When variations in GCK and YKT6 were used as a model of prediabetes, this genetically determined prediabetes increased microalbuminuria. Multiple logistic regression analyses revealed that fasting glucose concentration in plasma and SNP rs2908289 in GCK were associated with microalbuminuria, and adjustment for age, gender, smoking history, systolic blood pressure, waist circumference, and serum triglyceride levels did not attenuate this association. Our results suggest that prediabetes and the associated SNPs may predispose to microalbuminuria before the diagnosis of diabetes mellitus. Further studies are needed to explore the details of the physiological and molecular mechanisms underlying this genetic association.
Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
Jong Wook
JW
Choi
Division of Endocrinology and Metabolism, Hallym University College of Medicine, Seoul, South Korea.
Shinje
S
Moon
Korea Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, Korea.
Eun Jung
EJ
Jang
Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
Chang Hwa
CH
Lee
Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
Joon-Sung
JS
Park
D000328:Adult; D017677:Age Distribution; D000419:Albuminuria / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D000081410:Germinal Center Kinases; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011236:Prediabetic State / Q000453:epidemiology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D050683:R-SNARE Proteins / Q000235:genetics; D055105:Waist Circumference / Q000235:genetics / Q000502:physiology
D000081410:Germinal Center Kinases; D050683:R-SNARE Proteins; C491482:YKT6 protein, human; D017346:Protein Serine-Threonine Kinases