The contribution of genetic variants of SLC2A1 gene in T2DM and T2DM-nephropathy: association study and meta-analysis

• Published in: Renal failure 2018-11, Vol.40 (1), p.561-576
• Main Authors: Stefanidis, I., Tziastoudi, M., Tsironi, E. E., Dardiotis, E., Tachmitzi, S. V., Fotiadou, A., Pissas, G., Kytoudis, K., Sounidaki, M., Ampatzis, G., Mertens, P. R., Liakopoulos, V., Eleftheriadis, T., Hadjigeorgiou, G. M, Santos, M., Zintzaras, E.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alleles; Case-Control Studies; Clinical Study; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetic Nephropathies - genetics; diabetic nephropathy; Dominance; Female; Gene Frequency; Genetic diversity; Genetic Predisposition to Disease; genetic variants of SLC2A1; Genetic Variation; Glucose transporter; glucose transporter 1 (GLUT1); Glucose Transporter Type 1 - genetics; Haplotypes; Heredity; Humans; Logistic Models; Male; Meta-analysis; Middle Aged; Nephropathy; Risk Factors
• ISSN: 0886-022X; 1525-6049
• DOI: 10.1080/0886022X.2018.1496931

An association study was conducted to investigate the relation between 14 variants of glucose transporter 1 gene (SLC2A1) and the risk of type 2 diabetes (T2DM) leading to nephropathy. We also performed a meta-analysis of 11 studies investigating association between diabetic nephropathy (DN) and SLC2A1 variants. The cohort included 197 cases (T2DM with nephropathy), 155 diseased controls (T2DM without nephropathy) and 246 healthy controls. The association of variants with disease progression was tested using generalized odds ratio (OR G ). The risk of type 2 diabetes leading to nephropathy was estimated by the OR of additive and co-dominant models. The mode of inheritance was assessed using the degree of dominance index (h-index). We synthesized results of 11 studies examining association between 5 SLC2A1 variants and DN. OR G was used to assess the association between variants and DN using random effects models. Significant results were derived for co-dominant model of rs12407920 [OR = 2.01 (1.17-3.45)], rs841847 [OR = 1.73 (1.17-2.56)] and rs841853 [OR = 1.74 (1.18-2.55)] and for additive model of rs3729548 [OR = 0.52 (0.29-0.90)]. The mode of inheritance for rs12407920, rs841847 and rs841853 was 'dominance of each minor allele' and for rs3729548 'non-dominance'. Frequency of one haplotype (C-G-G-A-T-C-C-T-G-T-C-C-A-G) differed significantly between cases and healthy controls [p = .014]. Regarding meta-analysis, rs841853 contributed to an increased risk of DN [(OR G  = 1.43 (1.09-1.88); OR G  = 1.58 (1.01-2.48)] between diseased controls versus cases and healthy controls versus cases, respectively. Further studies confirm the association of rs12407920, rs841847, rs841853, as well as rs3729548 and the risk of T2DM leading to nephropathy.