Abstract
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.