Genetic Variants Relate to Fasting Plasma Glucose, 2-Hour Postprandial Glucose, Glycosylated Hemoglobin, and BMI in Prediabetes

Abstract

Diabetes mellitus (DM) is a chronic disease that seriously threatens human health. Prediabetes is a stage in the progression of DM. The level of clinical indicators including fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG), and glycosylated hemoglobin (HbA1C) are the diagnostic markers of diabetes. In this genome-wide association study (GWAS), we aimed to investigate the association of genetic variants with these phenotypes in Hainan prediabetes. In this study, we recruited 451 prediabetes patients from the residents aged ≥18 years who participated in the National Diabetes Prevalence Survey of the Chinese Medical Association in 2017. The GWAS of FPG, 2hPG, HbA1C, and body mass index (BMI) in prediabetes was analyzed with a linear model using an additive genetic model with adjustment for age and sex. We identified that rs13052524 inMRPS6and rs62212118 inSLC5A3were associated with 2hPG in Hainan prediabetes (p= 4.35 × 10-6,p= 4.05 × 10-6, respectively). Another six variants in the four genes (LINC01648,MATN1,CRAT37, andSLCO3A1) were related to HbA1C. Moreover, rs11142842, rs1891298, rs1891299, and rs11142843 inTRPM3/TMEM2and rs78432036 inMLYCD/OSGIN1were correlated to BMI (allp< 5 × 10-6). This study is the first to determine the genome-wide association of FPG, 2hPG, and HbA1C, which emphasizes the importance of in-depth understanding of the phenotypes of high-value susceptibility gene markers in the diagnosis of prediabetes.