Association of ELMO1 Genetic Polymorphism (rs741301) with the Progression of Diabetic Kidney Disease in Balinese Patients with Type 2 Diabetes Mellitus

Anak Agung Istri Kaila Kirtaniya, Asri Lestarini, Pande Ayu Naya Kasih Permatananda, Anak Agung Sri Agung Aryastuti


Background: Diabetic kidney disease (DKD) is one of diabetes mellitus microvascular complications. Engulfment and cell motility 1 (ELMO1) protein interacts with dedicator of cytokinesis 180 (DOCK180) and cyclooxygenase (COX)-2, which affects gene expression in extracellular matrix (ECM) and causes glomerular damage in several mechanisms, such as ECM accumulation and renal tubules thickening. Single nucleotide polymorphism (SNP) rs741301 is one of the ELMO1 genetic polymorphisms involved in DKD. The aim of this study was to evaluate the association between ELMO1 rs741301 polymorphism and DKD in type 2 diabetes mellitus (T2DM) among Balinese.

Materials and methods: This study was an observational analytical study with case-control method. Subjects were divided into control and case groups comprising 40 subjects each. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of DNA from T2DM patients were performed to detect the polymorphism in ELMO1 rs741301. Genotype and allele distribution obtained from this study was analyzed by chi-square (χ2) test and Hardy-Weinberg equilibrium law (p<0.05; CI: 95%).

Results: There was no significant difference between genotype or allele distribution of ELMO1 rs741301 with DKD incidence. Genotype AA against GG had odds ratio (OR) of 0.793 (p=0.814), AG against GG had OR of 0.602 (p=0.674), and A allele against G allele had OR of 0.761 (p=0.509).

Conclusion: There is no significant relationship between ELMO1 rs741301 polymorphism and DKD in T2DM patients among Balinese.

Keywords: ELMO1 gene, diabetic kidney disease, polymorphism

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Kaul K, Tarr JM, Ahmad SI, Kohner EM, Chibber R. Introduction to diabetes mellitus. Adv Exp Med Biol. 2012; 771: 1–11, CrossRef.

Herawati E, Susanto A, Sihombing CN. Autoantibodies in diabetes mellitus. Mol Cell Biomed Sci. 2017; 1(2): 58-64, CrossRef.

International Diabetes Federation. Diabetes Atlas. 9th ed. Brussels: International Diabetes Federation; 2019, article.

Shimazaki A, Kawamura Y, Kanazawa A, Sekine A, Saito S, Tsunoda T, et al. Genetic variations in the gene encoding ELMO1 are associated with susceptibility to diabetic nephropathy. Diabetes. 2005; 54(4): 1171–8, CrossRef.

Cytoskeleton, Inc. Rac1 in Diabetes: To Good and Bad. Denver: Cytoskeleton Inc.; 2016, article.

Hathaway CK, Chang AS, Grant R, Kim H-S, Madden VJ, Bagnell CRJ, et al. High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy. Proc Natl Acad Sci U S A. 2016; 113(8): 2218–22, CrossRef.

Yang C, Sorokin A. Upregulation of fibronectin expression by COX-2 is mediated by interaction with ELMO1. Cell Signal. 2011; 23(1): 99–104, CrossRef.

Lestarini A, Aryastuti AASA, Witari NPD, Sutarka IW, Wardani NWS, Hastuti P, et al. MCP-1 serum levels were higher in patient with diabetic nephropathy among Balinese. Indian J Public Health Res Dev. 2020; 11(2): 1456-61, CrossRef.

Lestarini A, Aryastuti AASA, Yasa IWPS. Chemotactic cytokine receptor 5 genetic polymorphism in diabetic nephropathy of the type 2 diabetes mellitus. Indian J Public Health Res Dev. 2022; 13(1): 83–90, CrossRef.

Aryastuti AASA, Sintya E, Lestarini A, Witari NPD. Allele frequency of a common variants and two common loss-of-function variants in organic cation transporter 1 (OCT1) among Balinese diabetic patients. Biomed Pharmacol J. 2022; 15(1): 269–75, CrossRef.

Kwiendacz H, Nabrdalik K, Adamczyk P, Moczulski D, Moczulska H, Trautsolt W, et al. Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: A pilot study. Endokrynol Pol. 2020; 71(1): 66–72, CrossRef.

Kim S, Abboud HE, Pahl MV, Tayek J, Snyder S, Tamkin J, et al. Examination of association with candidate genes for diabetic nephropathy in a Mexican American population. Clin J Am Soc Nephrol. 2010; 5(6): 1072–8, CrossRef.

Hanson RL, Millis MP, Young NJ, Kobes S, Nelson RG, Knowler WC, et al. ELMO1 variants and susceptibility to diabetic nephropathy in American Indians. Mol Genet Metab. 2010; 101(4): 383–90, CrossRef.

Mehrabzadeh M, Pasalar P, Karimi M, Abdollahi M, Daneshpour M, Asadolahpour E, et al. Association between ELMO1 gene polymorphisms and diabetic nephropathy in an Iranian population. J Diabetes Metab Disord. 2016; 15: 43, CrossRef.

Yadav AK, Kumar V, Dutta P, Bhansali A, Jha V. Variations in CCR5, but not HFE, ELMO1, or SLC12A3, are associated with susceptibility to kidney disease in north Indian individuals with type 2 diabetes. J Diabetes. 2014; 6(6): 547–55, CrossRef.

Bayoumy NMK, El-Shabrawi MM, Leheta OF, Abo El-Ela AEDM, Omar HH. Association of ELMO1 gene polymorphism and diabetic nephropathy among Egyptian patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2020; 36(5): 1–6, CrossRef.

Mooyaart AL, Valk EJ, van Es LA, Bruijn JA, de Heer E, Freedman BI, et al. Genetic associations in diabetic nephropathy: A meta-analysis. Diabetologia. 2011; 54(3): 544-53, CrossRef.

Ramadhanti R, Helda H. Association of hypertension and chronic kidney disease in population aged ≥18 years old. Mol Cell Biomed Sci. 2021; 5(3): 137–44, CrossRef.

Pezzolesi MG, Krolewski AS. The genetic risk of kidney disease in type 2 diabetes. Med Clin North Am. 2013; 97(1): 91–107, CrossRef.

Alexanian A, Sorokin A. Cyclooxygenase 2: Protein-protein interactions and posttranslational modifications. Physiol Genomics. 2017; 49(11): 667–81, CrossRef.

Katoh H, Negishi M. RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature. 2003; 424(6947): 461–4, CrossRef.

Karar T, Alniwaider RA, Fattah MA, Al Tamimi W, Alanazi A, Qureshi S. Assessment of microalbuminuria and albumin creatinine ratio in patients with type 2 diabetes mellitus. J Nat Sci Biol Med. 2015; 6(Suppl 1): S89-92, CrossRef.

Aryani BR, Prabawa IMY, Saraswati MR. Peningkatan kadar mean platelet volume-lymphocyte ratio (MPVLR) terhadap resiko diabetik nefropati pada pasien dengan diabetes melitus tipe II (DM-2) di RSUP Sanglah, Bali, Indonesia. Intisari Sains Medis. 2020; 11(1): 328-32, CrossRef.

Kartika R, Wibowo H. Impaired function of regulatory T cells in type 2 diabetes mellitus. Mol Cell Biomed Sci. 2020; 4(1): 1–9, CrossRef.

Abramovs N, Brass A, Tassabehji M. Hardy-Weinberg equilibrium in the large scale genomic sequencing era. Front Genet. 2020; 11: 210, CrossRef.

Mariya SS, Dewi FNA, Hayes E, Villiandra, Paramastri YA, Iskandriati D, et al. Association of CCL7 promoter polymorphism with responsiveness to allergen in cynomolgus macaque model of asthma. Indones Biomed J. 2020; 12(2): 183–8, CrossRef.

Wei L, Xiao Y, Li L, Xiong X, Han Y, Zhu X, et al. The susceptibility genes in diabetic nephropathy. Kidney Dis. 2018; 4(4): 226–37, CrossRef.


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