Association of the Transcription Factor 7-Like 2 (TCF7L2) rs7903146 Polymorphism with the Risk of Diabetic Nephropathy: A Meta-Analysis

Abstract

Transcription factor 7-like 2 (TCF7L2) polymorphism plays an essential role in the occurrence and development of patients living with diabetes, but the current conclusions are inconsistent on the relationship between TCF7L2 polymorphism and the risk of diabetic nephropathy. This meta-analysis aims to explore the exact association between TCF7L2 rs7903146 locus polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were searched for studies on the relationship between single nucleotide polymorphism at TCF7L2 rs7903146 locus and susceptibility to diabetic nephropathy until January 10, 2022. The data were analyzed by Stata 15.0 software. A total of 7 articles were included, covering 1443 patients with diabetic nephropathy and 2129 diabetic non-nephropathy patients. The results showed that allele C at TCF7L2 rs7903146 locus, compared to allele T, the pooled odds ratio (OR)=0.69 (95% CI: 0.56–0.85, p≤0.05). In the dominant gene inheritance model, recessive gene inheritance model, homozygous genetic model, and heterozygous genetic model, the pooled OR was 0.47 (95% CI: 0.36–0.61), 0.63 (95% CI: 0.54–0.73), 0.39 (95% CI: 0.29–0.51), and 0.59 (95% CI: 0.45–0.78), respectively, and the differences were statistically significant. In conclusion, TCF7L2 rs7903146 polymorphism is associated with susceptibility to diabetic nephropathy. Allele T and genotype TT can increase the risk of diabetic nephropathy.

Key words

diabetes - diabetic complications - diabetic nephropathy - diabetic neuropathy

• References

• 1 Mitratza M, Kunst AE, Harteloh PPM. et al. Prevalence of diabetes mellitus at the end of life: an investigation using individually linked cause-of-death and medical register data. Diabetes Res Clin Pr 2020; 160: 108003
• 2 Wojtasik-Bakalarz J, Ruzsa Z, Rakowski T. et al. Impact of coronary artery disease and diabetes mellitus on the long-term follow-up in patients after retrograde recanalization of the femoropopliteal arterial region. J Diabetes Res 2019; 6036359
• 3 Svensson MK, Tyrberg M, Nyström L. et al. The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes incidence study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors. Diabetes Metab Res 2015; 31: 138-146
• 4 Galsgaard J, Persson F, Hansen TW. et al. Plasma high-sensitivity troponin T predicts end-stage renal disease and cardiovascular and all-cause mortality in patients with type 1 diabetes and diabetic nephropathy. Kidney Int 2017; 92: 1242-1248
• 5 Russo G, Piscitelli P, Giandalia A. et al. Atherogenic dyslipidemia and diabetic nephropathy. J Nephrol 2020; 33: 1001-1008
• 6 Liang G, Song L, Chen Z. et al. Fibroblast growth factor 1 ameliorates diabetic nephropathy by an anti-inflammatory mechanism. Kidney Int 2018; 93: 95-109
• 7 Zhuang Y, Niu F, Liu D. et al. Associations of TCF7L2 gene polymorphisms with the risk of diabetic nephropathy: Aa case-control study. Medicine 2018; 97: e8388
• 8 Lin YC, Chang YH, Yang SY. et al. Update of pathophysiology and management of diabetic kidney disease. J Formos Med Assoc 2018; 117: 1-14
• 9 Ahmad J. Management of diabetic nephropathy: recent progress and future perspective. Diabetes Metab Syndr 2015; 9: 343-358
• 10 Ding W, Xu L, Zhang L. et al. Meta-analysis of association between TCF7L2 polymorphism rs7903146 and type 2 diabetes mellitus. Bmc Med Genet 2018; 19: 38
• 11 Jin T, Liu L. The Wnt signaling pathway effector TCF7L2 and type 2 diabetes mellitus. Mol Endocrinol 2008; 22: 2383-2392
• 12 Shao W, Wang D, Chiang YT. et al. The Wnt signaling pathway effector TCF7L2 controls gut and brain proglucagon gene expression and glucose homeostasis. Diabetes 2013; 62: 789-800
• 13 Araoka T, Abe H, Tominaga T. et al. Transcription factor 7-like 2 (TCF7L2) regulates activin receptor-like kinase 1 (ALK1)/Smad1 pathway for development of diabetic nephropathy. Mol Cells 2010; 30: 209-218
• 14 Morgan MF, Salam RF, Rady NH. et al. The Association of transcription factor 7 like 2 gene polymorphism with diabetic nephropathy in patients with type 2 diabetes mellitus. Curr Diabetes Rev 2020; 16: 370-375
• 15 Wang S, Dong J, Huang L. Cytokine polymorphisms and predisposition to diabetic nephropathy: a meta-analysis. Int Arch Allergy Imm 2021; 182: 158-165
• 16 Guan H, Xia MD, Wang M. et al. Methylenetetrahydrofolate reductase genetic polymorphism and the risk of diabetic nephropathy in type 2 diabetic patients. Medicine 2020; 99: e21558
• 17 Song N, Yang S, Wang YY. et al. The impact of vitamin D receptor gene polymorphisms on the susceptibility of diabetic vascular complications: a meta-analysis. Genet Test Mol Bioma 2019; 23: 533-556
• 18 Wu SH, Chang-Hsun H, Pei D. et al. Association and interaction analyses of genetic variants in ADIPOQ, ENPP1, GHSR, PPARgamma and TCF7L2 genes for diabetic nephropathy in a Taiwanese population with type 2 diabetes. Nephrol Dial Transplant 2009; 24: 3360-3366
• 19 Ismail ManalFouad, Shaker OlfatGamil, Ashour Esmat. et al. Genetic variants associated with the risk of diabetic nephropathy. Jökull J 2015; 65: 449-576
• 20 Moher D, Liberati A, Tetzlaff J. et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Rev Esp Nutr Hum Die 2014; 18: 172-181
• 21 Stang A. critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-605
• 22 Hoaglin DC. Assessment of heterogeneity in meta-analyses. JAMA 2014; 312: 2286-2287
• 23 Brok J, Thorlund K, Wetterslev J. et al. Apparently conclusive meta-analyses may be inconclusive – Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses. Int J Epidemiol 2009; 38: 287-298
• 24 Hussain H, Ramachandran V, Ravi S. et al. TCF7L2 rs7903146 polymorphism and diabetic nephropathy association is not independent of type 2 diabetes – a study in a south Indian population and meta-analysis. Endokrynol Pol 2014; 65: 298-305
• 25 Fu LL, Lin Y, Yang ZL. et al. Association analysis of genetic polymorphisms of TCF7L2,CDKAL1,SLC30A8,HHEX genes and microvascular complications of type 2 diabetes mellitus. Chin. J Med Genet 2012; 29: 194-199
• 26 Buraczynska M, Swatowski A, Markowska-Gosik D. et al. Transcription factor 7-like 2 (TCF7L2) gene polymorphism and complication/comorbidity profile in type 2 diabetes patients. Diabetes Res Clin Pr 2011; 93: 390-395
• 27 Xue P, Cao H, Ma Z. et al. Transcription factor 7-like 2 gene-smoking interaction on the risk of diabetic nephropathy in Chinese Han population. Genes Environ 2021; 43: 26
• 28 Fan S, Meng J, Zhang L. et al. CAV1 polymorphisms rs1049334, rs1049337, rs7804372 might be the potential risk in tumorigenicity of urinary cancer: a systematic review and meta-analysis. Pathol Res Pract 2019; 215: 151-158
• 29 Sale MM, Smith SG, Mychaleckyj JC. et al. Variants of the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in an African-American population enriched for nephropathy. Diabetes 2007; 56: 2638-2642
• 30 Maeda S, Osawa N, Hayashi T. et al. Genetic variations associated with diabetic nephropathy and type II diabetes in a Japanese population. Kidney Int 2007; S43-S48
• 31 Benzing T, Simons M, Walz G. Wnt signaling in polycystic kidney disease. J Am Soc Nephrol 2007; 18: 1389-1398
• 32 Kawakami T, Ren S, Duffield JS. Wnt signalling in kidney diseases: dual roles in renal injury and repair. J Pathol 2013; 229: 221-231