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

Leweihua Lin,Huibiao Quan,Lu Lin,Tuanyu Fang,Kaining Chen,Qianying Ou,Huachuan Zhang

doi:10.3389/fendo.2022.778069

Leweihua Lin, Huibiao Quan + Show 5 more

Open Access

https://doi.org/10.3389/fendo.2022.778069

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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 in MRPS6 and rs62212118 in SLC5A3 were 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, and SLCO3A1) were related to HbA1C. Moreover, rs11142842, rs1891298, rs1891299, and rs11142843 in TRPM3/TMEM2 and rs78432036 in MLYCD/OSGIN1 were correlated to BMI (all p < 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.

Highlights

Diabetes mellitus (DM) is an endocrine metabolic disease caused by many pathogenic factors marked by elevated blood glucose, becoming a global public health problem [1, 2]
A total of 451 prediabetes patients including 216 men and 235 women from Hainan province were recruited to evaluate the association of fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG), HbA1C, and body mass index (BMI) with 1,752,717 genotyped single-nucleotide polymorphisms (SNPs) using a genome-wide association analysis
Can genetic variants affect the phenotypes in prediabetes? In this study, we performed genome-wide association study (GWAS) to determine the effect of genetic variants on FPG, 2hPG, HbA1C, and BMI in Hainan prediabetes

Summary

Introduction

Diabetes mellitus (DM) is an endocrine metabolic disease caused by many pathogenic factors (genetic and environmental factors included) marked by elevated blood glucose, becoming a global public health problem [1, 2]. There are about 100 million DM over the age of 20 in China, which is expected to increase to 143 million by 2035 [3]. Prediabetes is a special state between health and diabetes, in which blood glucose is elevated without meeting the diagnostic criteria for DM. Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are high risk factors for developing prediabetes and are defined as the level of fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG), and glycosylated hemoglobin (HbA1C) in diabetes [4]. People with prediabetes are more likely to develop T2D than the general population [5]

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