Association study of the ABCC8 gene variants with type 2 diabetes in south Indians

Abstract

BACKGROUND:The ABCC8 gene which encodes the sulfonylurea receptor plays a major role in insulin secretion and is a potential candidate for type 2 diabetes. The -3c → t (rs1799854) and Thr759Thr (C → T, rs1801261) single nucleotide polymorphisms (SNPs) of the ABCC8 gene have been associated with type 2 diabetes in many populations. The present study was designed to investigate the association of these two SNPs in an Asian Indian population from south India.MATERIALS AND METHODS:A total of 1,300 subjects, 663 normal glucose tolerant (NGT) and 637 type 2 diabetic subjects were randomly selected from the Chennai Urban Rural Epidemiology Study (CURES). The -3c → t and Thr759Thr were genotyped in these subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and a few variants were confirmed by direct sequencing.RESULTS:The frequency of the ‘t’ allele of the -3c → t SNP was found to be 0.27 in NGT and 0.29 in type 2 diabetic subjects (P = 0.44). There was no significant difference in the genotypic frequency between the NGT and type 2 diabetic group (P = 0.18). Neither the genotypic frequency nor the allele frequency of the Thr759Thr polymorphism was found to differ significantly between the NGT and type 2 diabetic groups.CONCLUSION:The -3c → t and the Thr759Thr polymorphisms of the ABCC8 gene were not associated with type 2 diabetes in this study. However, an effect of these genetic variants on specific unidentified sub groups of type 2 diabetes cannot be excluded.

Identification of SNP rs1799854 ABCC8 gene and blood glucose levels in patients with type 2 diabetes mellitus at Moewardi hospital Surakarta Solo

“…One treatment in T2DM is sulfonylurea which can decrease blood glucose levels by increasing insulin secretion (Gumantara and Oktarlina, 2017). Sulfonylurea will bind to sulfonylurea receptors (SUR) to regulate of insulin secretion from pancreatic beta cells encoded by the ABCC8 gene (Venkatesan et al, 2014).…”

“…Polymorphism of rs1799859 is located in the exons area, which there is a substitution from G allele to A allele (AGG → AGA), However, it did not make any changes (Haghverdizadeh et al, 2014). While polymorphism of rs1801261 is located in the exons area, where the SNP converts the C allele into the T allele (ACC → ACT), but does not cause changes in amino acid threonine in residue 759 (Thr759Thr) (Venkatesan et al, 2014) (Haghverdizadeh et al, 2014).…”

“…Polymorphism in rs757110 indicates similar T2DM risk in Europe and Japan, but no association was observed in the Han Chinese population (Qin et al, 2013). Another result in the South India population showed that the polymorphism ABCC8 gene rs1799854 (-3c→t) has no relationship with T2DM (Venkatesan et al, 2014). Research on the ABCC8 gene in T2DM patients in the Solo population has never been reported.…”

“…The track consists of four Kir6.2 forming subunits along with four sulfonylurea receptor subunits (SUR). SUR1 is a potassium channel sensitive to ATP in pancreatic beta cells (Venkatesan et al, 2014), and is encoded by the ATP Binding Cassette Subfamily C Member 8 )ABCC8) gene (Engwa et al, 2018). The mechanism of insulin release in β pancreatic cells starts when glucose entering the cells and resulting ATP that can bind to the KATP channel.…”

“…The ABCC8 gene encodes a protein that includes a member of the superfamily of ATP-binding cassette (ABC) transporters (Anonim, 2021). SUR1, which is encoded by the ABCC8 gene located on chromosome 11p15, is one of the causes of T2DM risk (Venkatesan et al, 2014). The ABCC8 gene, as a sulfonylurea receptor, helps regulate insulin by coding the SUR1 subunit protein from the K-ATP channel that plays a role in insulin secretion from pancreatic β cells.…”