Genetic variant of TGF-ß associated with decreased renal function in type II diabetes mellitus patient: single center pilot study in Indonesia

https://doi.org/10.19106/JMedSci005304202101

Anggelia Puspasari(1*), Elfiani Elfiani(2), Susan Tarawifa(3), Rina Nofri Enis(4), Asro Hayani(5)

(1) Departement of Medical Biology and Biochemistry, Faculty of Medicine and Health Sciences, Universitas Jambi, Jambi
(2) Departement of Internal Medicine, Faculty of Medicine and Health Sciences, Universitas Jambi, Jambi
(3) Departement of Anatomy, Faculty of Medicine and Health Sciences, Universitas Jambi, Jambi
(4) Departement of Anatomy, Faculty of Medicine and Health Sciences, Universitas Jambi, Jambi
(5) Faculty of Medicine and Health Sciences, Universitas Jambi, Jambi
(*) Corresponding Author

Abstract


The interaction between genetic factors, blood glucose and hypertension plays a role in the onset of diabetic kidney disease (DKD) in type II diabetes mellitus (T2DM). Genetic variation of TGF-ß1 is associated with renal complication in T2DM with varying results between ethnicities. The Jambi Malay ethnic, which is the majority ethnic in Jambi Province, is an area that reports an increased prevalence of T2DM with DKD as the most frequent microvascular complications. In addition, previous study reported controlling blood glucose not associated with DKD indicating genetic may have play a role in DKD in this population. Studies related to genetic variation and decreased kidney function in T2DM patients has never been performed in this ethnic group. This study aimed to investigate the role of TGF-ß genetic variation as risk factor for decreased renal function in T2DM patients from Jambi Malay ethnicity. We conducted a cross sectional study involving 70 patients with T2DM. The inclusion criteria for renal complication based on a decrease in the glomerular filtration rate (GFR) of less than 60 mL/min/1.73. The genotyping method used was amplification refractory mutation system polymerase chain reaction (ARMS-PCR) for TGF-β1 rs1800470 T/C. Bivariate and multivariate analysis was performed to analyze phenotype and genotype association. The result of bivariate analysis showed T2DM patients with genotype CT (p:0.006; OR:0.125; 95% CI:0.027-0.575) and CC (p:0.007; OR:0.104; 95% CI:0.020-0.546) or C allele carrier (p:0.003; OR:0.117; 95% CI:0.027-0.500) had lower risk for decreased renal function than TT genotype. Multivariate analysis that included blood pressure and age variables showed the same finding for CT (p:0.007; OR:0.086; 95% CI:0.014-0.508) and CC genotype (p:0.022; OR:0.115; 95% CI:0.018-0.731). It is concluded from this study that T2DM patients with genotype CT, CC and carrier allele C have a lower risk for suffering kidney complications than genotype TT.


Keywords


decline renal function; diabetes mellitus; genetic variant; TGF ß-1; T2DM renal complication.

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References

  1. oye DN, Magliano DJ, Nelson RG, Pavkov ME. The global epidemiology of diabetes and kidney disease. Adv Chronic Kidney Dis 2017; 25(2):121-132. https://doi.org/10.1053/j.ackd.2017.10.011
  2. Mihardja L, Delima D, Massie RGA, Karyana M, Nugroho P, Yunir E. Prevalence of kidney dysfunction in diabetes mellitus and associated risk factors among productive age Indonesian. J Diabetes Metab Disord 2018; 17(1):53-61. https://doi.org/10.1007/s40200-018-0338-6
  3. Kementrian Kesehatan RI. Laporan Nasional RISKESDAS 2018. Jakarta: Badan Penelitian dan Pengembangan Kesehatan. 2019;123-143.
  4. Kusdiyah E, Makmur MJ, Aras RBP. Karakteristik faktor-faktor risiko terjadinya komplikasi kronik nefropati diabetik dan atau penyakit pembuluh darah perifer pada penderita diabetes mellitus di RSUD Raden Mattaher tahun 2018. e-SEHAD. 2020; 1(1):19-32.
  5. Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease. Clin J Am Soc Nephrol 2017; 12(12):2032-45. https://doi.org/ 10.2215/CJN.11491116.
  6. Elfiani, Nasrul E, Yanwirasti, Ali Z, Puspasari A. Plasma level of the engulfment and cell motility protein-1 are associated with kidney damage in diabetic nephropathy: A single-centre pilot study in Indonesia population. Open Access Maced. J Med Sci 2020; 8(A). https://doi.org/10.3889/oamjms.2020.4276
  7. Persson F, Rossing P. Diagnosis of diabetic kidney disease: state of the art and future perspective. Kidney Int Suppl 2018; 8(1):2-7. https://doi.org/10.1016/j.kisu.2017.10.003
  8. Chang AS, Hathaway CK, Smithies O, Kakoki M. Transforming growth factor-ß1 and diabetic nephropathy. Am J Physiol Renal Physiol 2016; 310(8):F689-96. https://doi.org/10.1152/ajprenal.00502.2015
  9. Gomes KB, Rodrigues KF, Fernandes AP. The role of Transforming Growth Factor- ß in diabetic nephropathy. Int J Med Gen 2014; 180270:1-7. https://doi.org/10.1155/2014/180270
  10. Qiao Y, Chen Y, Pan Y, Ling W, Tian F, Zhang X, Zhao H. Changes of transforming growth factor ß 1 in patients with type 2 diabetes and diabetic nephropathy. Medicine 2017; 96(15):e6583. https://doi.org/10.1097/MD.0000000000006583
  11. Yamada Y, Miyauchi A, Goto J, Takagi Y, Okuizumi H, Kanematsu M, Hase M, Takai H, Harada A, Ikeda K. Association of a polymor-phism of the transforming growth factor-ß 1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res 1998; 13(10):1569-1576. https://doi.org/10.1359/jbmr.1998.13.10.1569
  12. Gewaltig J, Mangasser-Stephan K, Gartung C, Biesterfeld S, Gressner AM. Association of polymorphisms of the transforming growth factor-ß1 gene with the rate of progression of HCV-induced liver fibrosis. Clin Chim Acta 2002; 316(1-2):83-94. https://doi.org/10.1016/S0009-8981(01)00738-0
  13. Coll E, Cormand B, Campos B, González-Núñez D, Iñigo P, Botey A, et al. Association of TGF-beta1 polymorphisms with chronic renal disease. J Nephrol 2004; 17(6):794-9.
  14. Babel N, Gabdrakhmanova L, Hammer MH, Schoenemann C, Skrypnikov V, Poliak N, et al. Predictive value of cytokine gene polymorphisms for the development of end-stage renal disease. J Nephrol 2006; 19(6):802-7.
  15. El-Sherbini S, Shahen SM, Mosaad YM, Abdelgawad MS, Talaat RM. Gene polymorphism of transforming growth factor- ß1 in Egyptian patients with type 2 diabetes and diabetic nephropathy. Acta Biochim Biophys Sin 2013; 45(4):330-8. https://doi.org/10.1093/abbs/gmt003
  16. Raina P, Sikka R, Kaur R, Sokhi J, Matharoo K, Singh V, et al. Association of transforming growth factor beta-1 (TGF-β1) genetic variation with type 2 Diabetes and end stage renal disease in two large population samples from North India. OMICS 2015; 19(5):306-17. https://doi.org/10.1089/omi.2015.0005
  17. Valladares-Salgado A, Angeles-Martínez J, Rosas M, García-Mena J, Utrera-Barillas D, Gómez-Díaz R, et al. Association of polymorphisms within the transforming growth factor-β1 gene with diabetic nephropathy and serum cholesterol and triglyceride concentrations. Nephrology (Carlton) 2010; 15(6):644-8. https://doi.org/10.1111/j.1440-1797.2010.01302.x
  18. Mao S, Yan B, Zhang J, Mao S, Yan B, Zhang J. Association of transforming growth factor-β1 polymorphisms with the risk of chronic kidney diseases. Renal Failure 2015; 37(10):304-11. https://doi.org/10.3109/0886022X.2015.1077324
  19. Zhou T, Li HY, Zhong H, Zhong Z. Relationship between transforming growth factor-β1 and type 2 diabetic nephropathy risk in Chinese population. BMC Med Genet 2018; 19(1):201. https://doi.org/10.1186/s12881-018-0717-3
  20. Soelistijo SA, Novida H, Rudijanto A, Soewondo P, Suastika K, Manaf A, Sanusi H, dkk. Konsesus pengelolaan dan pencegahan diabetes melitus tipe 2 di Indonesia 2015. PERKENI. 2015.
  21. Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV. ARMS-PCR methodologies to determine IL-10, TNF-alpha, TNF-beta and TGF-beta 1 gene polymorphisms. Transpl Immunol 1999; 7(2):127-8. https://doi.org/10.1016/s0966-3274(99)80030-6
  22. Hussain S, Jamali MC, Habib A, Hussain MS, Akhtar M, Najmi AK. Diabetic kidney disease: An overview of prevalence, risk factors, and biomarkers. Clin Epidemiol Glob Health 2021; (9):2-6. https://doi.org/10.1016/j.cegh.2020.05.016
  23. Crilly A, Hamilton J, Clark CJ, Jardine A, Madhok R. Analysis of transforming growth factor beta1 gene polymorphisms in patients with systemic sclerosis. Ann Rheum Dis 2002; 61(8):678-81. https://doi.org/10.1136/ard.61.8.678
  24. Ehnert S, Linnemann C, Braun B, Botsch J, Leibiger K, Hemmann P, et al. One-step ARMS-PCR for the detection of SNPs - Using the example of the PADI4 Gene. Methods Protoc 2019; 2(3):63. https://doi.org/10.3390/mps2030063
  25. Felipe R, Medrano V, Andre de Oliveira C. Guidelines for the Tetra-primer ARMS - PCR technique development. Mol Biotechnol 2014; 56(7):599-608. https://doi.org/10.1007/s12033-014-9734-4



DOI: https://doi.org/10.19106/JMedSci005304202101

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Journal of the Medical Sciences (Berkala Ilmu Kedokteran) by  Universitas Gadjah Mada is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
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