Association of rs11643718SLC12A3and rs741301ELMO1Variants with Diabetic Nephropathy in South Indian Population

Abstract

This study reports on the association of genetic variants selected from previous genome-wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30-2.30, P = 1.72 × 10 ) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.

Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study

“…The GWAS study has shown that the rs741301 polymorphism of the ELMO1 gene is a candidate diagnostic gene for DKD. We chose rs741301 polymorphism of ELMO1 gene as a candidate gene for DKD based upon findings from previous studies, but these prior studies are contradictory [12,[20][21][22][23][24][25][26][27][28][29]. To the best of our knowledge, none of the prior studies assessed the role of the ELMO1 gene with DKD among Polish patients.…”

“…Subsequent studies confirmed the association of different SNP variants in the ELMO1 gene with susceptibility to DKD in patients from various populations: African Americans [20], European Americans [21], American Indians [22], Mexican Americans [23], Tunisian Arabs [24], as well as citizens of China [25], India [26][27], Iran [28], and Malaysia [29]. Unfortunately, it is impossible to draw a unified conclusion from the outcomes because these studies were different in terms of methodology and definition of DKD.…”

“…Some of these patients presented with T2DM [20,[22][23][24][25][26][27][28][29], but others with type 1 diabetes mellitus [21]. Some of the authors used the DKD definition according to ADA [3,28] whereas others according to NKF [12,21,25,26,30]. This discrepancy may be caused by a lack of coherence between DKD definitions across leading international diabetology and nephrology associations [3,30].…”

Association of MMP-9 polymorphisms with diabetic nephropathy risk

“…[ 11 , 12 ] In DM-DN, genetic susceptibility is mainly characterized by familial aggregation, and the prevalence of DN is different among different ethnic groups. [ 13 , 14 ] Recently, due to the development of genetic methods, multiple single nucleotide polymorphisms (SNPs) associated with DN susceptibility have been discovered, such as SLC12A3, [ 15 ] ACACβ, [ 16 ] AGTR1, [ 16 ] ELMO1, [ 17 , 18 ] MTHFR, [ 19 ] SLC12A3, [ 20 ] CNDP1, and CNDP2. [ 21 ] The matrix metallopeptidase-9 (MMP-9) gene is also one of the widely studied SNPs in DN.…”

Engulfment and cell motility protein 1 potentiates diabetic cardiomyopathy via Rac-dependent and Rac-independent ROS production

“…In a genome-wide case control association study, Shimazaki et al found that a single nucleotide polymorphism in the 18th intron of the ELMO1 gene is strongly associated with diabetic nephropathy in Japanese (3). Since then the association has been observed between the polymorphisms in the ELMO1 gene and diabetic nephropathy in Whites (4,5), Chinese (6), African Americans (7), Pima Indians (8), South Indians (9), and Iranians (10).…”