Association of CCL2, CCR5, ELMO1, and IL8 Polymorphism with Diabetic Nephropathy in Malaysian Type 2 Diabetic Patients

Abstract

The unique variants or biomarkers of individuals help to understand the pathogenesis as well as the potential risk of individuals or patients to diabetic nephropathy (DN). The aim of this study was to investigate the association of a genetic polymorphism of monocyte chemoattractant protein-1 (CCL2-rs3917887), chemokine receptor 5 (CCR5-rs1799987), engulfment and cell mortality (ELMO1-rs74130), and interleukin-8 (IL8-rs4073) with the development of DN among Malaysian type 2 diabetes mellitus (T2DM) patients. More than one thousand diabetic patients were examined and a total of 652 T2DM patients were tested comprising 227 Malays (nonnephrotic=96 and nephrotic=131), 203 Chinese (nonnephrotic=95 and nephrotic=108), and 222 Indians (nonnephrotic=136 and nephrotic=86). DNA Sequenom mass ARRAY was employed to identify polymorphisms in CCL2, CCR5, ELMO1, and IL8 genes. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models and the best mode of inheritance was chosen. CCR5 rs1799987 (G>A) showed strong association with the development of diabetic nephropathy only among the Chinese with OR=6.71 (2.55-17.68) 95% CI while IL8 rs4073 (T>A) showed association with nephropathy only among the Indians with OR=1.57 (0.66-3.71) 95% CI. The additive model was the best model for the mode of inheritance of all the genes. The contribution of genetic variants differs across ethnic groups or background. Further studies which involve environmental risk factors should be taken into consideration.

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

“…They noticed a higher incidence of rs741301 in patients with diabetes compared to healthy controls, but there was no association of this variant with DKD [27]. Similarly, Yahya et al examined 820 patients from Malaysia and concluded that SNP rs741301 does not contribute to DKD [29].…”

“…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.…”

“…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].…”

Chemokine Receptor 5, a Double-Edged Sword in Metabolic Syndrome and Cardiovascular Disease

“…The mutations in the CCR5 gene promoter region (CCR5 59029 G to A alteration) and deletion of 32 nucleotides (CCR5-D32) lead to genetic inactivation of CCR5 (Nazir et al, 2014). Previous studies have found that CCR5-59029 G/A was an independent risk factor for DKD (Yahya et al, 2019). The CCR5 59029A-positive genotype was correlated with an increased risk for albuminuria (Zhang et al, 2016).…”