Gene polymorphism of transforming growth factor-β1 in Egyptian patients with type 2 diabetes and diabetic nephropathy

Abstract

Role of the transforming growth factor-b1 (TGF-b1) gene polymorphisms located at codons 10 and 25 in the genetic predisposition to type 2 diabetes (T2D) and in diabetic nephropathy (DN) in Egyptian patients was investigated. A case control study was done for 99 unrelated Egyptian patients with T2D (50 DN 2 and 49 DN 1) and 98 age-and sex-matched healthy controls. TGF-b1 T869C (codon 10) and G915C (codon 25) polymorphism detection was done by amplification refractory mutation system method. DN 1 patients were younger, with higher body mass index, serum triglycerides, serum creatinine, and lower serum albumin than those in DN 2 patients. Moderate and bad grades of diabetic control were associated with DN (P < 0.001). The TGF-b1 (T869C) C allele, TC and TC 1 CC genotypes were significantly higher in patients; the T allele and TT genotype were significantly higher in controls (Pc < 0.001). The TGF-b1 TC genotype was associated with DN (Pc < 0.05). Non-significant differences were detected between T2D patients and controls in the frequencies of TGF-b1 (G915C) alleles and genotypes. In conclusion, these preliminary data showed that the TGFb1 codon 10 C allele, and C allele-containing genotypes may be susceptible, and T allele/TT genotype may be protective factors for T2D and DN 1 complications.

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

“…Further genetic model analysis also revealed that the CC genotype provided a higher risk as compared to the TC + CC genotype combination for ESRD manifestation. Similar trends were reported by a study on an Egyptian population where frequency of C-allele was higher in cases (both total T2D and T2D with ESRD) as compared to controls, and the TC genotype was providing 2-2.7-fold risk towards T2D and ESRD development (El-Sherbini et al, 2013). TGF-b1 g.869T > C polymorphism was observed to provide risk towards DN in Mexican (Valladares-salgado et al, 2010) and Chinese populations (Wong et al, 2003) and towards ESRD in a North Indian population (Mittal and Manchanda, 2007).…”

The Susceptibility Genes in Diabetic Nephropathy

“…In renal diseases, elevated expression of TGF-β1 can induce renal hypertrophy and promote excessive accumulation of ECM proteins, thus leading to renal fibrosis [55]. To be more specific, TGF-β1 is significantly enhanced in the renal tissues of patients with DN, especially in mesangial cells of diabetic glomeruli [56]. Therefore, it is likely that these pathological changes caused by TGF-β1 may contribute to the initiation and progression of DN.…”

“…The hotspot mainly focuses on T869C (rs1800470; Leu10/Pro10; T29C, codon 10) in exon 1, which is located at position 10 in the signal peptide [55]. The T869C gene polymorphism has been linked with the risk of DN in different ethnic groups, such as Chinese [55], Egyptians [56], Mexicans [58], and Caucasians of Polish descent. The T869C gene polymorphism was notably different between diabetic patients with and without DN, and the DN group had a higher frequency of the CC/CT genotype [59].…”

“…The T869C gene polymorphism was notably different between diabetic patients with and without DN, and the DN group had a higher frequency of the CC/CT genotype [59]. C allele-containing genotypes may be susceptible, and the T allele/TT genotype may be a protective factor for DN [56, 58]. However, insignificant associations were also reported in Asians [60].…”

“…The G allele has also been associated with increased TGF-β1 production [61]. Valladares-Salgado et al [58] reported a positive association between the GC+CC genotypes of TGF-β1 G915C and DN in Mexicans, whereas El-Sherbini et al [56] found no statistically significant association in Egyptians. Zhang et al [62] also revealed that the G915C gene polymorphism was not associated with the risk of DN by conducting a meta-analysis that contained 7 studies.…”