Chauhan Tripty, Mittal R D, Mittal B
Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, UP India.
Department of Urology, SGPGIMS, Lucknow, UP India.
Indian J Clin Biochem. 2020 Jul;35(3):290-311. doi: 10.1007/s12291-019-00832-1. Epub 2019 May 15.
Numerous studies have investigated the relationship between various candidate gene polymorphisms and gallbladder stone disease (GSD) across ethnic populations; however, the results are often inconsistent. This meta-analysis aims to comprehensively evaluate the influence of common ABCG8 T400K, ABCG8 D19H, ABCG8 C54Y, ApoB100 EcoRI, ApoB100 XbaI, ApoE HhaI, CETP TaqI, CYP7A1 Bsa, LRPAP1 I/D and TNF-α A308G polymorphisms on the risk of gallbladder stone disease. 33 Full-text articles with 9250 cases and 12,029 healthy controls (total 21,279 subjects) were analyzed using the RevMan software (V5.1) and the Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) a Random-effects model was applied. Begg's funnel plots, Fail-safe number, Egger's regression intercept and Begg and Mazumdar rank correlation tests were performed for the potential publication bias and sensitivity analysis. The studies were also sub-grouped into European and non-European groups to find out role of ethnicity, if any, on GSD risk. Studies included in quantitative synthesis were ABCG8 T400K rs4148217 (cases/controls, n = 671/1416) (4 studies), ABCG8 D19H rs11887534 (n = 1633/2306) (8 studies), ABCG8 C54Y rs4148211 (n = 445/1194) (3 studies), ApoB100 EcoRI rs1042031 (n = 503/390) (4 studies), ApoB100 XbaI rs693 (n = 1214/1389) (9 studies), ApoE HhaI rs429358 (n = 1335/1482) (12 studies), CETP TaqI rs708272 (n = 1038/1025) (5 studies), CYP7A1 Bsa rs3808607 (n = 565/514) (3 studies), LRPAP1 I/D rs11267919 (n = 849/900) (3 studies), TNF-α A308G rs1800629 (n = 997/1413) (3 studies). The combined results displayed significant association of ABCG8 D19H (GC + CC) [OR with 95%CI = 2.2(1.7-2.8); < 0.00001], ABCG8 Y54C (GA + GG) [OR with 95%CI = 0.65(0.5-0.9); = 0.01]. APOB100 EcoRI (GG vs. AA) [OR with 95%CI = 0.51(0.3-0.9); = 0.05], (GG vs. GA) [OR with 95%CI = 0.6(0.4-0.9); = 0.04], (GA + AA) [OR with 95%CI = 0.6(0.4-0.9); = 0.006]. APOB Xba I (X vs. X) [OR with 95%CI = 0.53(0.3-0.8); = 0.006. APOE Hha I (E4/E4 vs. E3/E3) [OR with 95%CI = 3.5(1.1-14.9); = 0.04] and LRPAP1 I/D (ID + II) [OR with 95%CI = 1.27(1.0-1.6); = 0.03] with the GSD risk. It was found that ABCG D19H was significantly associated with GSD in both European and Non-European populations. While APOB XbaI and LRPAP1 I/D markers were associated with gallstone disease only in Non- European population. Additionally, APOE HhaI and APOB 100 ECoRI were found to be associated with GSD only in European population. The results of quantitative synthesis suggest that the ABCG8 D19H polymorphism was associated with the increased risk of GSD in both European and Non-European populations, APOE Hha I and LRPAP1 I/D polymorphisms were associated with the increased risk of GSD in European and Non-European population respectively. However, no association was found in ABCG8 T400K, CETP Taq1, CYP7A1 Bsa and TNF-A308G polymorphisms with Gallstone Disease.
众多研究探讨了不同种族人群中各种候选基因多态性与胆囊结石病（GSD）之间的关系；然而，结果往往不一致。本荟萃分析旨在全面评估常见的ABCG8 T400K、ABCG8 D19H、ABCG8 C54Y、ApoB100 EcoRI、ApoB100 XbaI、ApoE HhaI、CETP TaqI、CYP7A1 Bsa、LRPAP1 I/D和TNF-α A308G多态性对胆囊结石病风险的影响。使用RevMan软件（V5.1）和综合荟萃分析软件（版本2.0，BIOSTAT，新泽西州恩格尔伍德）对33篇全文文章进行分析，这些文章包含9250例病例和12029名健康对照（共21279名受试者），采用随机效应模型。进行Begg漏斗图、失效安全数、Egger回归截距以及Begg和Mazumdar等级相关检验以分析潜在的发表偏倚和敏感性。研究还被分为欧洲组和非欧洲组，以探究种族因素（若存在）对GSD风险的影响。纳入定量合成的研究包括ABCG8 T400K rs4148217（病例/对照，n = 671/1416）（4项研究）、ABCG8 D19H rs11887534（n = 1633/2306）（8项研究）、ABCG8 C54Y rs4148211（n = 445/1194）（3项研究）、ApoB100 EcoRI rs1042031（n = 503/390）（4项研究）、ApoB100 XbaI rs693（n = 1214/1389）（9项研究）、ApoE HhaI rs429358（n = 1335/1482）（12项研究）、CETP TaqI rs708272（n = 1038/1025）（5项研究）、CYP7A1 Bsa rs3808607（n = 565/514）（3项研究）、LRPAP1 I/D rs11267919（n = 849/900）（3项研究）、TNF-α A308G rs1800629（n = 997/1413）（3项研究）。合并结果显示ABCG8 D19H（GC + CC）[比值比（OR）及95%置信区间（CI）= 2.2（1.7 - 2.8）；P < 0.00001]、ABCG8 Y54C（GA + GG）[OR及95%CI = 0.65（0.5 - 0.9）；P = 0.01]、APOB100 EcoRI（GG vs. AA）[OR及95%CI = 0.51（0.3 - 0.9）；P = 0.05]、（GG vs. GA）[OR及95%CI = 0.6（0.4 - 0.9）；P = 0.04]、（GA + AA）[OR及95%CI = 0.6（0.4 - 0.9）；P = 0.006]、APOB Xba I（X vs. X）[OR及95%CI = 0.53（0.3 - 0.8）；P = 0.006]、APOE Hha I（E4/E4 vs. E3/E3）[OR及95%CI = 3.5（1.1 - 14.9）；P = 0.04]和LRPAP1 I/D（ID + II）[OR及95%CI = 1.27（1.0 - 1.6）；P = 0.03]与GSD风险相关。研究发现ABCG D19H在欧洲和非欧洲人群中均与GSD显著相关。而APOB XbaI和LRPAP1 I/D标记仅在非欧洲人群中与胆结石病相关。此外，APOE HhaI和APOB 100 ECoRI仅在欧洲人群中与GSD相关。定量合成结果表明，ABCG8 D19H多态性在欧洲和非欧洲人群中均与GSD风险增加相关，APOE Hha I和LRPAP1 I/D多态性分别在欧洲和非欧洲人群中与GSD风险增加相关。然而，未发现ABCG8 T400K、CETP Taq1、CYP7A1 Bsa和TNF - A308G多态性与胆结石病存在关联。
