μ阿片受体1基因rs1799971多态性和酒精依赖关系的Meta分析

doi:10.3969/j.issn.1004-583X.2021.04.002

摘要/Abstract

摘要：

目的探讨μ阿片受体1(OPRM1)基因rs1799971多态性和酒精依赖的关系。方法通过对PubMed、Web of Science、EMBASE、中国知网和万方电子数据库的检索,获取与研究目的相关的文献。截止时间为2020年7月10日。根据制定的纳入标准和排除标准筛选文献,用纽卡斯尔-渥太华量表(NOS)对纳入的研究进行质量评估。借助RevMan5.3软件对数据进行合并,计算出等位基因模型(A vs. G)、纯合子模型(AA vs. GG)、杂合子模型(AG vs. GG)、显性模型(AA+AG vs. GG)及隐性模型(AA vs. AG+GG)的P值、比值比(ORs)和95%可信区间(95%CIs)。结果本研究共纳入22篇文献,包括24项独立研究。NOS评分均在5分以上,提示纳入研究的方法学质量良好。结果显示总人群rs1799971多态性和酒精依赖的发生相关(P=0.03)。亚组分析结果表明这种相关性只存在于亚洲人群,具体表现为AG-基因型携带者发生酒精依赖的风险较高(P=0.02)。结论 OPRM1基因的rs1799971多态性和亚洲人群的酒精依赖风险存在相关性,AG-基因型携带者发生酒精依赖的风险较高。

关键词: 受体, 阿片样, μ, 多态性, 酒精依赖

Abstract:

Objective To investigate the association between rs1799971 polymorphism in mu opioid receptor 1 (OPRM1) gene and susceptibility of alcohol dependence. Methods Through five online databases including PubMed, Web of Science, EMBASE, CNKI, and Wanfang electronic database, the studies related to the research objective were accessed, and the search deadline was on July 10, 2020. And the selected literature is based on the established inclusion criteria and exclusion criteria, and the included studies subjects is assess the quality using the Newcastle-Ottawa Scale (NOS). The data was merged by RevMan5.3 software, the allele model (A vs. G), homozygous model (AA vs. GG), heterozygous model (AG vs. GG), dominance model (AA+AG vs. GG) and recessive model (AA vs. AG+GG) P value, odds ratio (ORs) and 95% confidence interval (95% CIs) was calculated. Results A total of 22 studies with 24 independent researches were included in the meta-analysis. All eligible studies received five or more NOS scores and were in favorable quality for the included methodology. The results suggested that rs1799971 polymorphism was associated with alcohol dependence (P=0.03). Subgroup analysis indicated the association only existed in the asian population. Especially AG-genotype carriers had an increased risk of alcohol dependence. Conclusion Rs1799971 polymorphism in OPRM1 gene is significantly associated with the risk of alcohol dependence in Asians, especially AG-genotype carriers have an elevated alcohol dependence risk.

Key words: receptors, opioid, mu, polymorphism, alcohol dependence

中图分类号:

R392.11

王玲丽, 赵志强, 靳新荣. μ阿片受体1基因rs1799971多态性和酒精依赖关系的Meta分析[J]. 临床荟萃, 2021, 36(4): 303-310.

Wang Lingli, Zhao Zhiqiang, Jin Xinrong. Association between rs1799971 polymorphism in mu opioid receptor 1 gene and susceptibility to alcohol dependence: a meta-analysis[J]. Clinical Focus, 2021, 36(4): 303-310.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2021.04.002

https://huicui.hebmu.edu.cn/CN/Y2021/V36/I4/303

图/表 9

参考文献 37

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作者	年份	国家	种族	性别(男:女) 病例组/对照组	诊断标准	研究类型	病例组基因型(例)			对照组基因型(例)			HWE P值	NOS评分 (分)
作者	年份	国家	种族	性别(男:女) 病例组/对照组	诊断标准	研究类型	AA	AG	GG	AA	AG	GG	HWE P值	NOS评分 (分)
Bergen AW(1)^[6]	1997	美国	高加索人	未报道/未报道	DSM-Ⅲ-R	病例-对照	19	1	0	45	15	0	0.269	8
Bergen AW(2)^[6]	1997	美国	高加索人	未报道/未报道	DSM-Ⅲ-R	病例-对照	104	34	2	144	39	1	0.340	8
Bergen AW(3)^[6]	1997	美国	高加索人	未报道/未报道	DSM-Ⅲ-R	病例-对照	162	68	8	96	30	3	0.290	8
Kim SA^[11]	2004	韩国	亚洲人	127:0/185:0	DSM-Ⅳ	病例-对照	46	47	7	54	53	21	0.202	6
Rommelspacher H^[12]	2001	德国	高加索人	282:45/未报道	ICD-10	病例-对照	262	62	33	289	48	43	0.001	6
Kim SG^[13]	2004	韩国	亚洲人	106:6/80:60	DSM-Ⅳ	病例-对照	37	61	14	68	57	15	0.559	5
Koller G^[14]	2012	德国	高加索人	1403:442/ 935:928	DSM-Ⅳ	病例-对照	1461	353	31	1417	419	27	0.528	7
Loh el W^[15]	2004	中国	亚洲人	149:9/ 147:2	DSM-Ⅲ-R	病例-对照	59	77	18	70	56	22	0.061	6
Miranda R^[16]	2010	美国	高加索人	9:18/ 89:71	DSM-Ⅳ	病例-对照	13	11	3	134	22	4	0.016	8
Sander T^[17]	1998	德国	高加索人	未报道/未报道	ICD-10	病例-对照	261	62	4	289	49	2	0.961	8
Franke P^[18]	2001	德国	高加索人	未报道/未报道	DSM-Ⅲ-R	病例-对照	170	50	1	284	74	7	0.403	8
Türkan H^[19]	2019	土耳其	高加索人	87: 16/ 58:25	DSM-Ⅳ	病例-对照	25	12	0	69	14	0	0.402	6
Park CI^[20]	2020	韩国	亚洲人	314: 0/ 324:0	DSM-Ⅳ	病例-对照	125	144	43	127	142	54	0.188	7
Ragia G^[21]	2016	希腊	高加索人	72: 0/ 74:0	DSM-Ⅳ	病例-对照	55	17	0	59	15	0	0.332	6
Gegenhuber B^[22]	2018	德国	高加索人	113:87/133:107	ICD-10	病例-对照	158	40	2	185	52	3	0.760	8
Zhang H^[23]	2006	美国	高加索人	未报道/未报道	DSM-Ⅳ	病例-对照	246	68	4	256	78	4	0.014	7
Deb I^[24]	2010	印度	亚洲人	53:0/82:0	DSM-Ⅳ	病例-对照	16	32	5	44	30	8	0.397	6
Schinka JA^[25]	2002	美国	高加索人	未报道/未报道	DSM-Ⅳ	病例-对照	152	27	0	262	93	5	0.309	7
Cupic B^[26]	2013	克罗地亚	高加索人	354:0/234:0	ICD-10	病例-对照	275	75	4	266	87	4	0.288	7
Nishizawa D^[27]	2006	日本	亚洲人	50: 8/ 23:51	DSM-Ⅳ	病例-对照	12	37	15	26	33	15	0.450	6
Bart G^[28]	2005	瑞士	高加索人	281:108/82:88	DSM-Ⅲ-R	病例-对照	299	90	0	147	23	0	0.344	7
Konjevod M^[29]	2020	克罗地亚	高加索人	303:56/ 373:49	DSM-Ⅳ	病例-对照	271	84	4	323	86	13	0.019	6
Gürel? C^[30]	2016	土耳其	高加索人	124:0/118:0	DSM-Ⅳ	病例-对照	97	22	2	88	28	1	0.446	7
Rouvinen-Lagerstr?m N^[31]	2013	芬兰	高加索人	未报道/未报道	DSM-Ⅳ	队列研究	325	152	26	320	157	29	0.102	8

作者	年份	国家	种族	性别(男:女) 病例组/对照组	诊断标准	研究类型	病例组基因型(例)			对照组基因型(例)			HWE P值	NOS评分 (分)
作者	年份	国家	种族	性别(男:女) 病例组/对照组	诊断标准	研究类型	AA	AG	GG	AA	AG	GG	HWE P值	NOS评分 (分)
Bergen AW(1)^[6]	1997	美国	高加索人	未报道/未报道	DSM-Ⅲ-R	病例-对照	19	1	0	45	15	0	0.269	8
Bergen AW(2)^[6]	1997	美国	高加索人	未报道/未报道	DSM-Ⅲ-R	病例-对照	104	34	2	144	39	1	0.340	8
Bergen AW(3)^[6]	1997	美国	高加索人	未报道/未报道	DSM-Ⅲ-R	病例-对照	162	68	8	96	30	3	0.290	8
Kim SA^[11]	2004	韩国	亚洲人	127:0/185:0	DSM-Ⅳ	病例-对照	46	47	7	54	53	21	0.202	6
Rommelspacher H^[12]	2001	德国	高加索人	282:45/未报道	ICD-10	病例-对照	262	62	33	289	48	43	0.001	6
Kim SG^[13]	2004	韩国	亚洲人	106:6/80:60	DSM-Ⅳ	病例-对照	37	61	14	68	57	15	0.559	5
Koller G^[14]	2012	德国	高加索人	1403:442/ 935:928	DSM-Ⅳ	病例-对照	1461	353	31	1417	419	27	0.528	7
Loh el W^[15]	2004	中国	亚洲人	149:9/ 147:2	DSM-Ⅲ-R	病例-对照	59	77	18	70	56	22	0.061	6
Miranda R^[16]	2010	美国	高加索人	9:18/ 89:71	DSM-Ⅳ	病例-对照	13	11	3	134	22	4	0.016	8
Sander T^[17]	1998	德国	高加索人	未报道/未报道	ICD-10	病例-对照	261	62	4	289	49	2	0.961	8
Franke P^[18]	2001	德国	高加索人	未报道/未报道	DSM-Ⅲ-R	病例-对照	170	50	1	284	74	7	0.403	8
Türkan H^[19]	2019	土耳其	高加索人	87: 16/ 58:25	DSM-Ⅳ	病例-对照	25	12	0	69	14	0	0.402	6
Park CI^[20]	2020	韩国	亚洲人	314: 0/ 324:0	DSM-Ⅳ	病例-对照	125	144	43	127	142	54	0.188	7
Ragia G^[21]	2016	希腊	高加索人	72: 0/ 74:0	DSM-Ⅳ	病例-对照	55	17	0	59	15	0	0.332	6
Gegenhuber B^[22]	2018	德国	高加索人	113:87/133:107	ICD-10	病例-对照	158	40	2	185	52	3	0.760	8
Zhang H^[23]	2006	美国	高加索人	未报道/未报道	DSM-Ⅳ	病例-对照	246	68	4	256	78	4	0.014	7
Deb I^[24]	2010	印度	亚洲人	53:0/82:0	DSM-Ⅳ	病例-对照	16	32	5	44	30	8	0.397	6
Schinka JA^[25]	2002	美国	高加索人	未报道/未报道	DSM-Ⅳ	病例-对照	152	27	0	262	93	5	0.309	7
Cupic B^[26]	2013	克罗地亚	高加索人	354:0/234:0	ICD-10	病例-对照	275	75	4	266	87	4	0.288	7
Nishizawa D^[27]	2006	日本	亚洲人	50: 8/ 23:51	DSM-Ⅳ	病例-对照	12	37	15	26	33	15	0.450	6
Bart G^[28]	2005	瑞士	高加索人	281:108/82:88	DSM-Ⅲ-R	病例-对照	299	90	0	147	23	0	0.344	7
Konjevod M^[29]	2020	克罗地亚	高加索人	303:56/ 373:49	DSM-Ⅳ	病例-对照	271	84	4	323	86	13	0.019	6
Gürel? C^[30]	2016	土耳其	高加索人	124:0/118:0	DSM-Ⅳ	病例-对照	97	22	2	88	28	1	0.446	7
Rouvinen-Lagerstr?m N^[31]	2013	芬兰	高加索人	未报道/未报道	DSM-Ⅳ	队列研究	325	152	26	320	157	29	0.102	8

遗传模型	遗传关联			研究数量	异质性检验		统计模型
遗传模型	OR值	95%CI	P值	研究数量	I²(%)	P值	统计模型
总人群
A vs. G	0.93	0.82 ~ 1.05	0.24	24	65	<0.01	R
AA vs. GG	1.06	0.87 ~ 1.28	0.56	20	24	0.16	F
AG vs. GG	1.25	1.03 ~ 1.53	0.03	20	0	0.63	F
AA+AG vs. GG	1.15	0.96 ~ 1.38	0.14	20	0	0.47	F
AA vs. AG+GG	0.87	0.74 ~ 1.02	0.08	24	68	<0.01	R
亚洲人
A vs. G	0.87	0.69 ~ 1.10	0.25	6	60	0.03	R
AA vs. GG	1.03	0.76 ~ 1.39	0.85	6	46	0.10	F
AG vs. GG	1.43	1.06 ~ 1.92	0.02	6	0	0.73	F
AA+AG vs. GG	1.21	0.92 ~ 1.59	0.18	6	0	0.48	F
AA vs. AG+GG	0.69	0.48 ~ 1.01	0.06	6	64	0.02	R
高加索人
A vs. G	0.95	0.81 ~ 1.10	0.48	18	67	<0.01	R
AA vs. GG	1.08	0.84 ~ 1.39	0.55	14	17	0.55	F
AG vs. GG	1.13	0.86 ~ 1.47	0.39	14	0	0.52	F
AA+AG vs. GG	1.09	0.85 ~ 1.40	0.49	14	5	0.40	F
AA vs. AG+GG	0.93	0.78 ~ 1.11	0.43	18	67	<0.01	R
男/女性混合
A vs. G	0.89	0.76 ~ 1.05	0.17	17	72	<0.01	R
AA vs. GG	1.00	0.80 ~ 1.25	1.00	14	31	0.13	F
AG vs. GG	1.21	0.96 ~ 1.53	0.11	14	0	0.55	F
AA+AG vs. GG	1.09	0.87 ~ 1.36	0.45	14	5	0.39	F
AA vs. AG+GG	0.97	0.89 ~ 1.06	0.56	17	74	<0.01	R
男性
A vs. G	1.02	0.89 ~ 1.17	0.77	9	17	0.29	F
AA vs. GG	1.18	0.83 ~ 1.69	0.36	8	0	0.54	F
AG vs. GG	1.31	0.92 ~ 1.87	0.21	8	0	0.64	F
AA+AG vs. GG	1.26	0.90 ~ 1.77	0.17	8	0	0.65	F
AA vs. AG+GG	0.98	0.83 ~ 1.15	0.77	9	25	0.2	F

遗传模型	遗传关联			研究数量	异质性检验		统计模型
遗传模型	OR值	95%CI	P值	研究数量	I²(%)	P值	统计模型
总人群
A vs. G	0.93	0.82 ~ 1.05	0.24	24	65	<0.01	R
AA vs. GG	1.06	0.87 ~ 1.28	0.56	20	24	0.16	F
AG vs. GG	1.25	1.03 ~ 1.53	0.03	20	0	0.63	F
AA+AG vs. GG	1.15	0.96 ~ 1.38	0.14	20	0	0.47	F
AA vs. AG+GG	0.87	0.74 ~ 1.02	0.08	24	68	<0.01	R
亚洲人
A vs. G	0.87	0.69 ~ 1.10	0.25	6	60	0.03	R
AA vs. GG	1.03	0.76 ~ 1.39	0.85	6	46	0.10	F
AG vs. GG	1.43	1.06 ~ 1.92	0.02	6	0	0.73	F
AA+AG vs. GG	1.21	0.92 ~ 1.59	0.18	6	0	0.48	F
AA vs. AG+GG	0.69	0.48 ~ 1.01	0.06	6	64	0.02	R
高加索人
A vs. G	0.95	0.81 ~ 1.10	0.48	18	67	<0.01	R
AA vs. GG	1.08	0.84 ~ 1.39	0.55	14	17	0.55	F
AG vs. GG	1.13	0.86 ~ 1.47	0.39	14	0	0.52	F
AA+AG vs. GG	1.09	0.85 ~ 1.40	0.49	14	5	0.40	F
AA vs. AG+GG	0.93	0.78 ~ 1.11	0.43	18	67	<0.01	R
男/女性混合
A vs. G	0.89	0.76 ~ 1.05	0.17	17	72	<0.01	R
AA vs. GG	1.00	0.80 ~ 1.25	1.00	14	31	0.13	F
AG vs. GG	1.21	0.96 ~ 1.53	0.11	14	0	0.55	F
AA+AG vs. GG	1.09	0.87 ~ 1.36	0.45	14	5	0.39	F
AA vs. AG+GG	0.97	0.89 ~ 1.06	0.56	17	74	<0.01	R
男性
A vs. G	1.02	0.89 ~ 1.17	0.77	9	17	0.29	F
AA vs. GG	1.18	0.83 ~ 1.69	0.36	8	0	0.54	F
AG vs. GG	1.31	0.92 ~ 1.87	0.21	8	0	0.64	F
AA+AG vs. GG	1.26	0.90 ~ 1.77	0.17	8	0	0.65	F
AA vs. AG+GG	0.98	0.83 ~ 1.15	0.77	9	25	0.2	F