Association between A1166C Polymorphism of the Angiotensin II Type-1 Receptor Gene and Type-2 Diabetic Nephropathy in an Indonesian Malay Population

Zulkhair Ali, Ida Kusrini, Alwi Shahab, Irsan Saleh

Abstract


Background: diabetic nephropathy (DN) is the leading cause of blood dialysis worldwide and a major etiology of End-Stage Renal Disease cases in Indonesia. Previous studies showed a relevant link between A1166C polymorphism of Angiotensin II Type-1 Receptor (AT1R) gene and glomerular hyper-filtration as a part of pathogenesis of DN. The aim of this study was to elaborate the association between A1166C AT1R polymorphism and susceptibility of individual with type-2 diabetes to DN in Malay Indonesian population. Methods: a case-control study of 120 consecutive patients with type-2 diabetes mellitus (40 patients in each groups for macro-albuminuria, micro-albuminuria, and normo-albuminuria) was conducted for A1166C AT1R gene polymorphism. The A1166C polymorphism of the AT1R gene was determined based on PCR/RFLP. Results: the mutant C allele was found in 5%, 13.75%, and 12.5% in normo-, micro-, and macro-albuminuria patients respectively. The heterozygote AC genotype was found significantly higher in micro-albuminuria, compared to normo-albuminuria group. Heterozygote AC genotype (OR 3.2 [1.01-10.08], p=0.03) and C allele (OR 2.8[0.95-8.67], p=0.038) were significantly higher in DN, indicating A1166C AT1R gene polymorphism as a risk factor for DN in Malay Indonesian population with type-2 diabetes. Conclusion: there was positive association between A1166C AT1R polymorphism and susceptibility of type-2 diabetics to DN in Malay Indonesian Population. It also indicated that the A1166C AT1R polymorphism could play a role in early pathogenesis of DN.

Keywords


angiotensin II type-1 receptor; polymorphism; diabetic nephropathy

References


Ghaderian SB, Hayati F, Shayanpour S, Mousavi SS. Diabetes and end-stage renal disease; a review article on new concepts. J Renal Inj Prev. 2015;4(2):28.

Perhimpunan Nefrologi Indonesia. 8th Report of Indonesian renal registry. Jakarta: Pernefri; 2015.

John S. Complication in diabetic nephropathy. Diabetes Metab Syndr. 2016;10(4):247-9.

Al-Rubeaan K, Youssef AM, Subhani SN. Diabetic nephropathy and its risk factors in a society with a type 2 diabetes epidemic: a Saudi National Diabetes Registry-based study. PloS one. 2014;9(2):e88956.

Conserva F, Gesualdo L, Papale M. A systems biology overview on human diabetic nephropathy: from genetic susceptibility to post-transcriptional and post-translational modifications. J Diabetes Res. 2016;2016.

Tarnow L, Cambien F, Rossing P, et al. Angiotensin-II type 1 receptor gene polymorphism and diabetic microangiopathy. Nephrol Dial Transplant. 1996;11(6):1019-23.

Thomas WG. Regulation of angiotensin II type 1 (AT1) receptor function. Regul Pept. 1999;79(1):9-23.

El-Aziz TA, Hussein YM, Mohamed RH, Shalaby SM. Renin–angiotensin system genes polymorphism in Egyptians with premature coronary artery disease. Gene. 2012;498(2):270-5.

Buraczynska M, Ksiazek P, Zaluska W, et al. Angiotensin II type 1receptor gene polymorphism in end-stage renal disease. Nephron. 2002;92:51–5.

Miller JA, Thai K, Scholey JW. Angiotensin II type 1 receptor gene polymorphism predicts response to losartan and angiotensin II. Kidney Int. 1999;56(6):2173-80.

Paolo Palatini; Glomerular hyperfiltration: a marker of early renal damage in pre-diabetes and pre-hypertension. Nephrol Dial Transplant. 2012;27(5):1708-14.

Fradin S, Goulet-Salmon B, Chantepie M, et al. Relationship between polymorphisms in the renin-angiotensin system and nephropathy in type 2 diabetic patients. J Diabetes Metab. 2002.

Moradi M, Rahimi Z, Amiri S, et al. AT1R A1166C variants in patients with type 2 diabetes mellitus and diabetic nephropathy. J Nephropathol. 2015;4(3):69.

Chang HR, Cheng CH, Shu KH, et al. Study of the polymorphism of angiotensinogen, anigiotensin-converting enzyme and angiotensin receptor in type II diabetes with end-stage renal disease in Taiwan. J Chin Med Assoc. 2003;66(1):51-6.

American Diabetes Association. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Supplement 1):S13-27.

Soelistijo SA, Novida H, Rudijanto A, et al. Konsensus pengelolaan dan pencegahan diabetes melitus tipe 2 di Indonesia 2015. PB. PERKENI. 2015.

Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

Doria A, Onuma T, Warram JH, Krolewski AS. Synergistic effect of angiotensin II type 1 receptor genotype and poor glycaemic control on risk of nephropathy in IDDM. Diabetologia. 1997;40(11):1293-9.

Duncan JA, Scholey JW, Miller JA. Angiotensin II type 1 receptor gene polymorphisms in humans: physiology and pathophysiology of the genotypes. Curr Opin Nephrol Hypertens. 2001;10(1):111-6.

Siragy HM. Angiotensin AT1 and AT2 receptors - the battle for health and disease. Nephrol Dial Transplant. 2007:22(11):3128–30.

Suzuki K, Han GD, Miyauchi N, et al. Angiotensin II type 1 and type 2 receptors play opposite roles in regulating the barrier function of kidney glomerular capillary wall. Am J Pathol. 2007;170(6):1841-53.

Khalilpourfarshbafi M, Hajiaghaalipour F, Selvarajan KK, Adam A. Mesenchymal stem cell-based therapies against podocyte damage in diabetic nephropathy. J Tissue Eng Regen Med. 2017;14(3):201-10.


Full Text: PDF

Refbacks

  • There are currently no refbacks.


Copyright (c) 2019 Acta Medica Indonesiana