Journal of Nephropathology (Oct 2018)

Association of rs7903146 polymorphism in the TCF7L2 gene with diabetic nephropathy and decreased estimated GFR in an Arab population in southwest Iran

  • Ali Karimi Akhormeh,
  • Mehrnoosh Zakerkish,
  • Hamid Yaghooti,
  • Narges Mohammadtaghvaei,
  • Mohammad Taha Jalali,
  • Ramin Tavakoli

DOI
https://doi.org/10.15171/jnp.2018.54
Journal volume & issue
Vol. 7, no. 4
pp. 273 – 280

Abstract

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Background: Transcription factor 7-like 2 (TCF7L2) acts as a downstream effector in the Wnt signaling pathway. It plays important roles in the proliferation and differentiation of islet betacell, insulin secretion and kidney development. Objectives: This study aimed to demonstrate whether rs7903146 variant is associated with diabetic nephropathy (DN) and measures of kidney function in a diabetic and healthy Arab population in southwest of Iran. Patients and Methods: This study is comprised of 132 diabetic subjects (T2DM) and 66 healthy participants. The diabetic subgroups were composed of patients with DN (n=56) and early onset of diabetes (n=71). The rs7903146 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in all the participants. Blood glucose, HbA1c, blood urea nitrogen (BUN), creatinine and urinary albumin were evaluated by a biochemistry analyzer and enzyme-linked immunosorbent assay (ELISA) was employed for cystatin C measurement. Results: The frequency of genotypes was significantly different between all the diabetic cases and control subjects (P<0.05). The TT variant odds ratio (OR) versus CT/CC genotypes for diabetes was 2.47 (95% CI 1.11-5.48). An association was observed between TT homozygous and DN (OR for TT 2.78, 1.13-6.84). Early onset diabetic patients showed stronger association (OR: 4.64, 1.64-13.14, P=0.003). The TT genotype was also found to be a risk variant for decreased estimated glomerular filtration rate (eGFR)(Cys-Cr) below 60 mL/min/1.73 m2 (OR: 3.36, 1.4-8.1, P=0.005). Conclusions: The results confirmed that the TCF7L2 gene rs7903146 variants are significantly associated with T2DM in Arab population of Iran. The TT genotype of this SNP is also predisposed to the risk of developing DN especially in subjects with early onset diabetes. Patients with TT genotype were also at risk of decreased GFR.

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