成年男性葡萄糖-6-磷酸脱氢酶活性低下与乙型肝炎病毒感染的关联性研究

关婷; 张月; 张东梅; 杨娟; 马旭; 赵君

doi:10.16766/j.cnki.issn.1674-4152.002766

成年男性葡萄糖-6-磷酸脱氢酶活性低下与乙型肝炎病毒感染的关联性研究

doi: 10.16766/j.cnki.issn.1674-4152.002766

关婷¹,
张月²,
张东梅¹,
杨娟¹,
马旭²,
赵君^2, ,

1.
深圳市卫生健康发展研究中心，广东深圳 518028
2.
国家卫生健康委科学技术研究所，国家人类遗传资源中心，北京 100081

基金项目:

国家重点研发计划课题 2016YFC1000307

国家卫生健康委科学技术研究所所级课题 2018NRIFPJ03

详细信息

通讯作者:
赵君, E-mail: zj@e-health.org.cn

中图分类号: R512.62
计量
- 文章访问数: 197
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- 被引次数: 0
出版历程
- 收稿日期: 2021-12-11
- 网络出版日期: 2023-02-07

Association of low glucose-6-phosphate dehydrogenase enzyme activity with hepatitis B virus infection in adult males

1.
Shenzhen Health Development Research Center, Shenzhen, Guangdong 518028, China

摘要

摘要: 目的探讨成年男性葡萄糖-6-磷酸脱氢酶(G6PD)活性低下与乙型肝炎病毒(HBV)感染的关系。方法采用病例对照研究方法，以2013年1月—2019年12月间85 286例参加深圳市免费孕前优生健康检查且符合纳入与排除标准的成年男性为研究对象。采用logistic回归分析研究成年男性G6PD活性低下与HBV感染的关系，以及两者对谷丙转氨酶(ALT)升高的影响。结果与非G6PD活性低下的成年男性相比，G6PD活性低下者HBV感染的风险增加20.4%(OR=1.204, P＜0.001)。与非G6PD活性低下且没有HBV感染的成年男性相比，仅HBV感染者ALT轻度和中/重度升高的风险分别增加60.3%(OR=1.603, P＜0.001)和123.8%(OR=2.238, P＜0.001)，而G6PD活性低下合并HBV感染者ALT轻度和中/重度升高的风险分别增加69.3%(OR=1.693, P＜0.001)和190.2%(OR=2.902, P＜0.001)。结论成年男性G6PD活性低下会增加HBV感染风险，且会增加HBV感染者ALT升高的风险。临床中如遇G6PD活性低下合并HBV感染的成年男性，应探索2种疾病的协同管理方法。
- 葡萄糖-6-磷酸脱氢酶 /
- 乙型肝炎病毒 /
- 成年男性
Abstract: Objective To investigate the association between low glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and hepatitis B virus (HBV) infection in adult males. Methods A case-control study was conducted on 85 286 adult males who participated in the National Free Pre-conception Health Checkup Project in Shenzhen from January 2013 to December 2019 and met the inclusion and exclusion criteria. The relationship between low G6PD enzyme activity and HBV infection was analysed by multivariate logistic regression models, and their influence on glutamic-pyruvic transaminase (ALT) elevation was observed. Results Adult males with a low G6PD enzyme activity had a 20.4% (OR=1.204, P < 0.001) increased risk of HBV infection compared with those with non-low G6PD enzyme activity. Compared with adult males without low G6PD enzyme activity and without HBV infection, those with HBV infection alone had a 60.3% (OR=1.603, P < 0.001) and 123.8% (OR=2.238, P < 0.001) increased risk of mild and moderate/severe elevation of ALT, respectively. Meanwhile, those with combined low G6PD enzyme activity and HBV infection had 69.3% (OR=1.693, P < 0.001) and 190.2% (OR=2.902, P < 0.001) increased risk of mild and moderate/severe elevation of ALT, respectively. Conclusion Adult males with a low G6PD enzyme activity will increase the risk of HBV infection, and increase the risk of elevated ALT in HBV-infected individuals. In the case of adult males with a low G6PD enzyme activity and HBV infection, the collaborative management method of the two diseases must be explored for clinical settings.
- Glucose-6-phosphate dehydrogenase /
- Hepatitis B virus /
- Adult males

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表 1 HBV感染组和对照组研究人群基本特征[例(%)]

Table 1. Basic characteristics of participants in HBV infection group and control group[cases (%)]

项目	对照组 (n=55 219)	HBV感染组 (n=30 067)	统计量	P值
年龄(岁)			-32.038^b	＜0.001
18~25	5 697(10.32)	1 603(5.33)
26~30	25 844(46.80)	12 487(41.53)
31~35	15 287(27.68)	10 054(33.44)
≥36	8 391(15.20)	5 923(19.70)
民族			106.540^c	＜0.001
汉族	53 298(97.14)	29 414(98.29)
少数民族	1 570(2.86)	512(1.71)
职业			91.909^c	＜0.001
教师/公务员/职员	23 613(44.24)	13 525(46.38)
工人	16 779(31.43)	8 335(28.58)
服务业	5 075(9.51)	2 859(9.80)
经商	4 257(7.97)	2 566(8.80)
其他^a	3 656(6.85)	1 874(6.43)
文化程度			-12.929^c	＜0.001
大专/本科及以上	35 865(66.06)	20 849(70.44)
高中及以下	18 423(33.94)	8 751(29.56)
饮酒			745.020^c	＜0.001
是	33 052(60.15)	15 100(50.44)
否	21 893(39.85)	14 838(49.56)
吸烟			338.510^c	＜0.001
是	17 691(32.22)	7 825(26.15)
否	37 218(67.78)	22 095(73.85)
BMI			-16.259^b	＜0.001
正常体重	28 593(52.56)	17 058(57.62)
体重过低	2 662(4.89)	1 466(4.95)
超重	17 800(32.72)	9 052(30.57)
肥胖	5 342(9.82)	2 030(6.86)
自报注射过乙肝疫苗			1 496.200^c	＜0.001
是	22 298(40.38)	8 147(27.10)
否	37 218(67.78)	22 095(73.85)
妻子HBsAg(+)			750.520^c	＜0.001
是	2 427(4.65)	2 763(9.56)
否	49 819(95.35)	26 131(90.44)
G6PD活性低下			73.662^c	＜0.001
是	4 374(7.92)	2 899(9.64)
否	50 845(92.08)	27 168(90.36)
注：^a其他职业包括农民、无业等；^b为Z值，^c为χ²值。民族、职业、文化程度、饮酒、吸烟、BMI、妻子HBsAg(+)均存在缺失值。

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表 2 G6PD活性低下与HBV感染的关联性亚组分析

Table 2. Subgroup analysis of the association between low G6PD enzyme activity and HBV infection

亚组	类别	例数^b	B	SE	Wald χ²	P值	OR(95% CI)
年龄(岁)	18~25	6 001	0.157	0.105	1.493	0.135	1.170(0.949~1.434)
	26~30	35 094	0.192	0.041	4.697	＜0.001	1.212(1.118~1.313)
	31~35	22 999	0.179	0.048	3.712	＜0.001	1.196(1.088~1.314)
	≥36	12 720	0.182	0.062	2.921	0.003	1.200(1.062~1.356)
民族	汉族	74 617	0.188	0.027	6.895	＜0.001	1.207(1.144~1.273)
	少数民族	1 213	0.067	0.182	0.369	0.712	1.070(0.743~1.520)
职业	教师/公务员/职员	33 401	0.148	0.042	3.494	＜0.001	1.159(1.067~1.259)
	工人	19 111	0.134	0.048	2.817	0.005	1.143(1.041~1.255)
	服务业	4 677	0.146	0.080	1.818	0.069	1.157(0.988~1.354)
	经商	3 771	0.362	0.092	3.950	＜0.001	1.436(1.199~1.717)
	其他^a	2 119	0.403	0.102	3.947	＜0.001	1.497(1.224~1.828)
文化程度	大专/本科和以上	52 569	0.207	0.034	6.126	＜0.001	1.230(1.151~1.314)
	高中和以下	21 449	0.143	0.045	3.191	0.001	1.154(1.057~1.260)
饮酒	是	43 225	0.223	0.037	6.050	＜0.001	1.249(1.162~1.343)
	否	32 783	0.141	0.040	3.568	＜0.001	1.151(1.065~1.244)
吸烟	是	22 297	0.211	0.050	4.256	＜0.001	1.233(1.120~1.360)
	否	53 603	0.178	0.032	5.536	＜0.001	1.194(1.122~1.272)
BMI	正常体重	40 180	0.149	0.036	4.153	＜0.001	1.160(1.082~1.244)
	体重过低	2 357	0.399	0.116	3.446	＜0.001	1.490(1.187~1.869)
	超重	23 582	0.223	0.049	4.518	＜0.001	1.249(1.134~1.376)
	肥胖	5 563	0.176	0.096	1.837	0.066	1.193(0.987~1.438)
自报注射过乙肝疫苗	是	28 121	0.125	0.051	2.451	0.014	1.133(1.024~1.251)
	否	48 693	0.201	0.032	6.292	＜0.001	1.222(1.148~1.301)
妻子HBsAg(+)	是	749	0.206	0.095	2.159	0.031	1.229(1.020~1.483)
	否	67 773	0.184	0.028	6.549	＜0.001	1.202(1.138~1.270)
注：^a其他职业包括农民、无业等其他职业。^b该亚组中实际模型运行所包含的例数。

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表 3 G6PD活性低下及HBV感染对ALT升高的影响

Table 3. Effects of low G6PD enzyme activity and HBV infection on ALT elevation

变量	ALT正常 (例)	ALT轻度升高						ALT中/重度升高
变量	ALT正常 (例)	例数	B	SE	Wald χ²	P值	OR^a(95% CI)	例数	B	SE	Wald χ²	P值	OR^a(95% CI)
HBsAg(-) G6PD(-)	42 960	6 333						1 543
HBsAg(-) G6PD(+)	3 671	570	0.090	0.050	1.778	0.075	1.094(0.999~1.206)	131	0.069	0.097	0.709	0.478	1.071(0.882~1.289)
HBsAg(+) G6PD(-)	21 221	4 492	0.472	0.024	19.957	＜0.001	1.603(1.530~1.679)	1 446	0.805	0.042	19.238	＜0.001	2.238(2.061~2.429)
HBsAg(+) G6PD(+)	2 230	486	0.527	0.056	9.446	＜0.001	1.693(1.517~1.887)	182	1.066	0.087	12.342	＜0.001	2.902(2.444~3.429)
注：^a调整因素包括年龄、民族、职业、文化程度、饮酒、吸烟、BMI、自报注射过乙肝疫苗、妻子HBsAg(+)。

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参考文献(26)

[1]	陶子馨, 朱安娜, 杨芳. 葡萄糖-6-磷酸脱氢酶缺乏症研究进展[J]. 中国产前诊断杂志(电子版), 2019, 11(3): 49-53. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGCQ201903012.htm TAO Z X, ZHU A N, YANG F. Progress in research on glucose-6-phosphate dehydrogenase deficiency[J]. Chinese Journal of Prenatal Diagnosis (Electronic Version), 2019, 11(3): 49-53. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGCQ201903012.htm
[2]	唐芳, 唐诚芳, 蒋翔, 等. 广州新生儿葡萄糖-6-磷酸脱氢酶缺乏症基因型与酶活性关联分析[J]. 中华预防医学杂志, 2020, 54(11): 1275-1282. TANG F, TANG C F, JIANG X, et al. Correlation analysis of genotypes and the enzymatic activities of glucose-6-phosphate dehydrogenase in neonates in Guangzhou[J]. Chinese Journal of Preventive Medicine, 2020, 54(11): 1275-1282.
[3]	李丽梅, 彭华保, 李丽霞, 等. 新生儿葡萄糖-6-磷酸脱氢酶缺乏症临床特点分析[J]. 现代医药卫生, 2016, 32(1): 100-102. doi: 10.3969/j.issn.1009-5519.2016.01.036 LI L M, PENG H B, LI L X, et al. The clinical characters of glucose-6-phosphate dehydrogenase deficiency in neonate[J]. Journal of Modern Medicine & Health, 2016, 32(1): 100-10 doi: 10.3969/j.issn.1009-5519.2016.01.036
[4]	汪业胜, 王胜难, 潘金花, 等. 我国2009—2018年病毒性肝炎的发病趋势分析和预测研究[J]. 中华流行病学杂志, 2020, 41(9): 1460-1464. WANG Y S, WANG S N, PAN J H, et al. Trend analysis and prediction of viral hepatitis incidence in China, 2009-2018[J]. Chinese Journal of Epidemiology, 2020, 41(9): 1460-1464.
[5]	毛宝宏, 王燕侠, 周丽, 等. 孕期HBV感染及肝内胆汁淤积症对小于胎龄儿与低出生体重的交互影响[J]. 中华疾病控制杂志, 2019, 23(1): 29-33. https://www.cnki.com.cn/Article/CJFDTOTAL-JBKZ201901007.htm MAO B H, WANG Y X, ZHOU L, et al. Intrahepatic cholestasis of pregnancy and hepatitis B virus infection during pregnancy elevates the risks of small for gestational age and low birth weight infant[J]. Chinese Journal of Disease Control & Prevention, 2019, 23(1): 29-33. https://www.cnki.com.cn/Article/CJFDTOTAL-JBKZ201901007.htm
[6]	AU W Y, CHAN S C. Association between glucose 6-phosphate dehydrogenase (G6PD) deficiency and fatal outcome of hepatitis E infection in middle-aged men[J]. Singapore Med J, 2012, 53(2): 148-149.
[7]	MOIZ B, ALI S A. Fulminant hemolysis in glucose-6-phosphate dehydrogenase deficiency[J]. Clin Case Rep, 2018, 6(1): 224-225.
[8]	LIN H R, WU Y H, YEN W C, et al. Diminished COX-2/PGE2-Mediated antiviral response due to impaired NOX/MAPK signaling in G6PD-Knockdown lung epithelial cells[J]. PLoS One, 2016, 11(4): e153462. DOI: 10.1371/journal.pone.0153462.
[9]	CAO Z Y, DING Y, CAO L, et al. Isochlorogenic acid C prevents enterovirus 71 infection via modulating redox homeostasis of glutathione[J]. Sci Rep, 2017, 7(1): 16278. DOI: 10.1038/s41598-017-16446-7.
[10]	肖鸽飞, 周玉球, 张旭华, 等. G6PD缺乏会增加乙型肝炎病毒感染吗?[J]. 中国优生与遗传杂志, 1997, 5(3): 92-96. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYYA199703054.htm XIAO G F, ZHOU Y Q, ZHANG X H, et al. Does G6PD deficiency increase the risk of hepatitis B virus?[J]. Chinese Journal of Birth Health & Heredity, 1997, 5(3): 92-96. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYYA199703054.htm
[11]	荆庆, 张克仁, 宋济洲, 等. 葡萄糖6磷酸脱氢酶缺陷者中的乙型肝炎感染[J]. 新医学, 1979, 10(8): 388. https://www.cnki.com.cn/Article/CJFDTOTAL-XYXX197908013.htm JING Q, ZHANG K R, SONG J Z, et al. The prevalence of hepatitis B virus in patients with glucose-6-phosphate dehydrogenase deficiency[J]. Journal of New Medicine, 1979, 10(8): 388. https://www.cnki.com.cn/Article/CJFDTOTAL-XYXX197908013.htm
[12]	ZHAO J, ZHANG X, GUAN T, et al. The association between low glucose-6-phosphate dehydrogenase activity level and hepatitis B virus infection among pre-pregnant reproductive-age Chinese females[J]. Sci Rep, 2019, 9(1): 3865. DOI: 10.1038/s41598-09-40354-7.
[13]	王德林. 乙型肝炎五项及其32种组合模式[M]. 北京: 科学普及出版社, 2003. WANG D L. Five markers of hepatitis B and their 32 combination patterns[M]. Beijing: Science Popularization Press, 2003.
[14]	宋文君, 黄文湧, 杨敬源, 等. 贵州省少数民族地区外出务工者乙型肝炎流行模式[J]. 中华疾病控制杂志, 2019, 23(10): 1255-1259. https://www.cnki.com.cn/Article/CJFDTOTAL-JBKZ201910021.htm SONG W J, HUANG W Y, YANG J Y, et al. A study on epidemic model of hepatitis B virus in migrant workers in Guizhou minority areas[J]. Chinese Journal of Disease Control & Prevention, 2019, 23(10): 1255-1259. https://www.cnki.com.cn/Article/CJFDTOTAL-JBKZ201910021.htm
[15]	黄馥菡, 赵湘, 姚炯, 等. 体质指数与性别差异对浙江中北部农村居民慢性肾脏病患病率的影响[J]. 中华全科医学, 2018, 16(9): 1462-1466. doi: 10.16766/j.cnki.issn.1674-4152.000400 HUANG F H, ZHAO X, YAO J, et al. The effects of body mass index and gender difference on the prevalence of chronic kidney disease in rural residents in north-central of Zhejiang[J]. Chinese Journal of General Practice, 2018, 16(9): 1462-1466. doi: 10.16766/j.cnki.issn.1674-4152.000400
[16]	彭凌, 杨柳青, 彭婷婷, 等. 替诺福韦酯阻断乙型肝炎病毒母婴传播不同停药时间的安全性评价[J]. 中华实验和临床感染病杂志(电子版), 2019, 13(1): 12-18. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSGR201901003.htm PENG L, YANG L Q, PENG T T, et al. Safety of withdrawal during treatment with tenofovir disoproxil of mothers and infants at various timepoints[J]. Chinese Journal of Experimental and Clinical Infectious Disease (Electronic Edition), 2019, 13(1): 12-18. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSGR201901003.htm
[17]	TSAI K J, HUNG I J, CHOW C K, et al. Impaired production of nitric oxide, superoxide, and hydrogen peroxide in glucose 6-phosphate-dehydrogenase-deficient granulocytes[J]. FEBS Lett, 1998, 436(3): 411-414.
[18]	COOPER M R, DECHATELET L R, MCCALL C E, et al. Complete deficiency of leukocyte glucose-6-phosphate dehydrogenase with defective bactericidal activity[J]. J Clin Invest, 1972, 51(4): 769-778.
[19]	EMOKPAE M A, MRAKPOR B A. Do sex differences in respiratory burst enzyme activities exist in human immunodeficiency virus-1 infection?[J]. Med Sci(Basel), 2016, 4(4): 19.
[20]	WU Y H, TSENG C P, CHENG M L, et al. Glucose-6-phosphate dehydrogenase deficiency enhances human coronavirus 229E infection[J]. J Infect Dis, 2008, 197(6): 812-816.
[21]	WU Y H, CHIU D T, LIN H R, et al. Glucose-6-Phosphate dehydrogenase enhances antiviral response through downregulation of NADPH sensor HSCARG and upregulation of NF-κB signaling[J]. Viruses, 2015, 7(12): 6689-6706.
[22]	KARKI P, MALIK S, MALLICK B, et al. Massive hemolysis causing renal failure in acute hepatitis E infection[J]. J Clin Transl Hepatol, 2016, 4(4): 345-347.
[23]	SHARMA D, SINGH O, JUNEJA D, et al. Hepatitis A virus-induced severe hemolysis complicated by severe glucose-6-phosphate dehydrogenase deficiency[J]. Indian J Crit Care Med, 2018, 22(9): 670-673.
[24]	MORROW R J, SMETANA H F, SAI F T, et al. Unusual features of viral hepatitis in Accra, Ghana[J]. Ann Intern Med, 1968, 68(6): 1250-1264.
[25]	王宗丽, 温平城. 病毒性肝炎与红细胞G-6-PD活性关系的初步探讨[J]. 右江民族医学院学报, 1992, 14(4): 285-288. https://www.cnki.com.cn/Article/CJFDTOTAL-YJMZ199204005.htm WANG Z L, WEN P C. Relationship between virus hepatitis and RBC G-6-PD[J]. Journal of Youjiang Medical College for National Minorities, 1992, 14(4): 285-288. https://www.cnki.com.cn/Article/CJFDTOTAL-YJMZ199204005.htm
[26]	刘运周, 曾学平, 肖洋. 病毒性肝炎患者葡萄糖-6-磷酸脱氢酶检测的临床意义[J]. 新乡医学院学报, 2008, 25(3): 307-309. https://www.cnki.com.cn/Article/CJFDTOTAL-XXYX200803039.htm LIU Y Z, ZHOU X P, XIAO Y. The clinical significance of glucose-6-phosphate dehydrogenase detection in patients with viral hepatitis[J]. Journal of Xinxiang Medical College, 2008, 25(3): 307-309. https://www.cnki.com.cn/Article/CJFDTOTAL-XXYX200803039.htm