ABCMdb

PMID: 25804128

Nicolas A, Fatima S, Lamri A, Bellili-Munoz N, Halimi JM, Saulnier PJ, Hadjadj S, Velho G, Marre M, Roussel R, Fumeron F
ABCG8 polymorphisms and renal disease in type 2 diabetic patients.
Metabolism. 2015 Jun;64(6):713-9. doi: 10.1016/j.metabol.2015.03.005. Epub 2015 Mar 14., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCG8 p.Asp19His ABCG8 p.Thr400Lys The ATP-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) play an important role in intestinal sterol absorption and bile acid secretion. The aim of our study was to assess the associations between two ABCG8 coding polymorphisms, T400K and D19H, and the incidence of renal events in type 2 diabetic subjects. Login to comment 12 ABCG8 p.Asp19His No significant association was found between the D19H polymorphism and the risk of diabetic nephropathy. Login to comment 33 ABCG8 p.Asp19His ABCG8 p.Thr400Lys In particular, the variants of ABCG8 D19H (rs11887534, G>C, exon 1) and ABCG8 T400K (rs4148217, C>A, exon 8) have been the most frequently reported to be associated with phenotypic variability. Login to comment 35 ABCG8 p.Asp19His ABCG8 p.Thr400Lys In the present investigation, we assessed associations of D19H and T400K variants in the coding region of ABCG8 with the incidence of severe kidney outcomes in the prospective DIABHYCAR cohort of French type 2 diabetic patients [27-30]. Login to comment 54 ABCG8 p.Asp19His ABCG8 p.Thr400Lys Polymorphism determination Polymorphisms T400K (rs4148217, C>A, exon 8) and D19H (rs11887534, G>C, exon 1) were genotyped using the Kaspar method (LGC Genomics, Hoddesdon, UK). Login to comment 71 ABCG8 p.Thr400Lys The characteristics of participants at baseline according to the incidence of renal events during 714 M E T A B O L I S M C L I N I C A L A N D E X P E R I M E N T A L 6 follow-upareshowninTable1.Thegenotypeswerenotsignificantly associated with any of the baseline characteristics of the patients, except a trend for an association between T400K and eGFR, the K allele being associated with a lower rate (eGFR in ml/mn/1.73 m2 : 81.7 (65.4-102.5), 81.1 (63.8-101.5) and 77.8 (63.6-96.7) for the TT, TK and KK genotypes, respectively, P = 0.08). Login to comment 75 ABCG8 p.Asp19His No significant association was found between the D19H polymorphism and the incidence of renal events (Table 2). Login to comment 77 ABCG8 p.Thr400Lys Validation population In order to validate our findings, we tested the ABCG8 T400K polymorphism in the DIAB2NEPHROGENE population. Login to comment 107 ABCG8 p.Asp19His ABCG8 p.Thr400Lys Since FXR is a bile acid receptor, it might interact with ABCG8 involved in bile acid secretion. The D19H polymorphism was not significantly associated with renal disease in our study, although its effects on plasma plant sterols and bile acid secretion seem of greater magnitude than those of T400K [22]. Login to comment 111 ABCG8 p.Asp19His ABCG8 p.Thr400Lys Polymorphism Renal event Statistics Without, n (%) With, n (%) Incidence, % P c7;2 unadjusted Hazard ratio (95% CI) Model 1 Model 2 a T400K (C>A) TT 1948 (64.9) 39 (52.0) 2.0 2 df: 0.018 Additive: 0.007 Dominant (CA + AA vs CC): 0.022 1.75 (1.20-2.56), P = 0.003 1.52 (1.05-2.21), P = 0.03 TK 953 (31.8) 30 (40.0) 3.1 KK 100 (3.3) 6 (8.0) 5.7 MAF 0.192 0.280 D19H (G>C) DD 2,615 (87.2) 69 (93.2) 2.6 2 df: 0.29 Additive: 0.13 Dominant (GC + CC vs GG): 0.14 0.53 (0.21-1.31), P = 0.16 0.53 (0.21-1.33), P = 0.18 DH 372 (12.4) 5 (6.8) 1.3 HH 11 (0.4) 0 (0) 0.0 MAF 0.066 0.034 MAF: minor allele frequency. a Cox regression analysis for the additive model, model 1: adjustment for sex, age, BMI, TG, total and HDL cholesterol, CRP, HbA1c, glycemia, diabetes duration, and prior myocardial infarction; model 2: idem + eGFR, UAE, SBP, DBP at baseline. Login to comment 122 ABCG8 p.Thr400Lys Nevertheless, the association of ABCG8 T400K polymorphism with renal disease was validated in the DIAB2NEPHROGENE population of patients with type 2 diabetes. Login to comment 145 ABCG8 p.Thr400Lys M. Marre (Bichat Hospital, Paris, France); steering committee: Table 4 - ABCG8 T400K (C>A) polymorphism genotype frequencies according to end-stage renal disease prevalence in DIAB2NEPHROGENE. Login to comment 146 ABCG8 p.Thr400Lys T400K (C>A) End-stage renal disease Statistics Without, n (%) With, n (%) Prevalence, % P c7;2 unadjusted Odds ratio (95% CI) a TT 1366 (65.5) 26 (49.1) 1.9 2 df: 0.028; additive: 0.05 Dominant (CA + AA vs CC): 0.015 Additive model 1 1.54 (0.99-2.38), P = 0.055 Additive model 2 1.63 (1.05-2.54), P = 0.03 TK 627 (30.0) 25 (47.2) 3.8 KK 94 (4.5) 2 (3.8) 2.1 MAF 0.195 0.273 Dominant model 1 2.01 (1.15-3.54), P = 0.015 Dominant model 2 2.22 (1.25-3.94), P = 0.007 MAF: minor allele frequency. a Logistic regression analysis, model 1: adjusted for sex, age, BMI, total cholesterol, HbA1c, diabetes duration and prior myocardial infarction. Login to comment 194 ABCG8 p.Met429Val [18] Miwa K, Inazu A, Kobayashi J, Higashikata T, Nohara A, Kawashiri M, et al. ATP-binding cassette transporter G8 M429V polymorphism as a novel genetic marker of higher cholesterol absorption in hypercholesterolaemic Japanese subjects. Login to comment