Genetic variation of rs3811463 is associated with gestational diabetes mellitus susceptibility

Abstract

Abstract. Gestational diabetes mellitus (GDM) is a growing health concern, and it increases the risk of adverse pregnancy outcomes with substantial long-term adverse health impacts on mothers and their offspring. Several studies have revealed specific associations between genetic variants and the risk of GDM. Single nucleotide polymorphisms (SNPs) are the major type of genetic variation in humans. Let-7 microRNA targets are enriched for genes containing SNPs associated with glucose metabolism, including Lin28. In the present study, the effect of T/C variants of rs3811463 (a SNP located near to the let-7 binding site in Lin28) on GDM risk was investigated. A GDM rat model was successfully constructed using a high fat diet and streptozotocin injection, and the primary skeletal muscle cells were isolated. The cell transfection results demonstrated that rs3811463-T/C significantly affected the glucose uptake and insulin sensitivity. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the C allele at rs3811463 regulated the expression of glucose metabolism-associated genes insulin-like growth factor two binding protein 2 and glucokinase. Western blot analysis data revealed that replacement of the T allele by the C allele at rs3811463 modulated the protein level of Sirtuin 1. Taken together, it was concluded that the let-7/Lin28 axis regulated glucose uptake and insulin sensitivity by modulating the expression of glucose metabolism-associated proteins. These findings provide novel evidence on the association between genetic variations of rs3811463 and GDM susceptibility.

RETRACTED ARTICLE: Interference of KLF9 relieved the development of gestational diabetes mellitus by upregulating DDAH2

“…GDM is a heterogeneous disorder that occurs during the pregnancy of women [ 16 ]. This disease has grown to be a burdensome health issue as it presents long-term consequences for offspring and consumes large expenditures for its treatment [ 17 , 18 ]. A better understanding of underlying mechanism pertaining to GDM may contribute to the identification of molecular targets for management of this disease.…”

RETRACTED: Polysaccharide IV from Lycium barbarum L. Improves Lipid Profiles of Gestational Diabetes Mellitus of Pregnancy by Upregulating ABCA1 and Downregulating Sterol Regulatory Element-Binding Transcription 1 via miR-33

“…Gestational diabetes mellitus (GDM), a special type of diabetes, is caused by multiple factors with genetic predisposition ( 1 ) and endocrine metabolic diseases ( 2 , 3 ). GDM is defined as the different glucose intolerance that occurs within the first trimester of pregnancy.…”

Growth-suppressor microRNAs mediate synaptic overgrowth and behavioral deficits in Fragile X mental retardation protein deficiency

“…Interestingly, an SNP in Lin28 (rs3811463; located near the regulatory let-7 binding site) that was previously identified by GWAS studies to confer increased risk for type II diabetes has been linked to gestational diabetes mellitus, which is a significant risk factor for ASD susceptibility in offspring. 147 …”