载脂蛋白E基因多态性及血脂水平与肺结核易感性分析

doi:10.19982/j.issn.1000-6621.20230111

中国防痨杂志 ›› 2023, Vol. 45 ›› Issue (8): 752-760.doi: 10.19982/j.issn.1000-6621.20230111

载脂蛋白E基因多态性及血脂水平与肺结核易感性分析

余志康¹^,², 熊娜婷¹^,³, 吴和明², 杜京津¹, 李凌¹^,⁴()

¹广东医科大学基础医学院,东莞 523808
²广东省梅州市人民医院(梅州市医学科学院)科研实验中心,梅州 514031
³广东省梅州市人民医院输血科,梅州 514031
⁴南方医科大学基础医学院,广州 510515

收稿日期:2023-04-14 出版日期:2023-08-10 发布日期:2023-08-09
通信作者: 李凌 E-mail:liling@smu.edu.cn
基金资助:
广东省基础与应用基础研究基金项目(2021A1515220106);梅州市人民医院科研培育项目(PY-C2020033)

Analysis of correlation between apolipoprotein E gene polymorphisms and lipid levels with susceptibility to pulmonary tuberculosis

Yu Zhikang¹^,², Xiong Nating¹^,³, Wu Heming², Du Jingjin¹, Li Ling¹^,⁴()

¹School of Basic Medical Science, Guangdong Medical University, Dongguan 523808, China
²Research Experiment Center, Meizhou People’s Hospital (Meizhou Academy of Medical Sciences), Guangdong Province, Meizhou 514031, China
³Blood Transfusion Department, Meizhou People’s Hospital, Guangdong Province, Meizhou 514031, China
⁴School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China

Received:2023-04-14 Online:2023-08-10 Published:2023-08-09
Contact: Li Ling E-mail:liling@smu.edu.cn
Supported by:
Guangdong Basic and Applied Basic Research Fund Project(2021A1515220106);Scientific Research and Cultivation Project of Meizhou People’s Hospital(PY-C2020033)

摘要/Abstract

摘要：

目的: 探讨载脂蛋白E (apolipoprotein E,ApoE)基因多态性及血脂水平与肺结核患病的相关性。方法: 采用回顾性研究方法,选取2016年1月1日至2020年12月12日梅州市人民医院诊断为肺结核的1118例患者作为病例组,选取同期于本院体检健康者582名作为对照组。收集研究对象的基本信息(年龄,性别)及实验室检验指标[包括血常规,甘油三酯(TG),总胆固醇(TC),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C),载脂蛋白A1(Apo-A1),载脂蛋白B(Apo-B),ApoE基因分型检测结果]。分析病例组与对照组ApoE基因型分布情况、血脂水平差异、ApoE基因型与血脂水平的相关性,并采用多因素logistic回归分析ApoE基因型及血脂水平对肺结核患病的影响。结果: 病例组的TG、TC、HDL-C、LDL-C、Apo-A1、Apo-B水平分别为:1.23(0.76,1.47)mmol/L、(4.18±1.17)mmol/L、(1.14±0.38)mmol/L、(2.36±0.82)mmol/L、(0.94±0.32)g/L、(0.79±0.26)g/L,均明显低于对照组[分别为1.64(1.07,2.06)mmol/L、(5.24±1.18)mmol/L、(1.36±0.34)mmol/L、(2.98±0.90)mmol/L、(1.31±0.33)g/L、(0.97±0.29)g/L],差异均有统计学意义(U=-12.603、t=17.605、t=12.096、t=13.784、t=22.614、t=12.071,P值均<0.001)。病例组中携带ApoE基因ε2/ε3基因型者的TG、TC、HDL-C、LDL-C、Apo-A1、Apo-B水平分别为1.21(0.73,1.38)mmol/L、(3.81±1.21)mmol/L、(1.17±0.36)mmol/L、(2.01±0.79)mmol/L、(0.96±0.32)g/L、(0.67±0.22)g/L,均明显低于对照组[分别为1.56(0.96,1.95)mmol/L、(4.78±1.03)mmol/L、(1.42±0.39)mmol/L、(2.50±0.81)mmol/L、(1.39±0.36)g/L、(0.83±0.28)g/L],差异均有统计学意义(U=-3.805、t=5.009、t=3.968、t=3.666、t=7.755、t=3.491,P值均<0.001)。病例组中携带ApoE基因ε2/ε3基因型者的TC、LDL-C、Apo-B水平分别为(3.81±1.21)mmol/L、(2.01±0.79)mmol/L、(0.67±0.22)g/L,均明显低于携带ε3/ε3基因型者[分别为(4.21±1.09)mmol/L、(2.40±0.76)mmol/L、(0.81±0.25)g/L],差异均有统计学意义(t值分别为0.471、5.595、5.681,P值均<0.001)。病例组ApoE基因ε2/ε3基因型频率[13.1%(146/1118)]明显高于对照组[8.4%(49/582)],差异有统计学意义(χ²=8.114,P=0.004);ε2等位基因频率[7.7%(174/2236)]明显高于对照组[5.8%(67/1164)],差异有统计学意义(χ²=4.770,P=0.029)。多因素logistic回归分析显示,携带ApoE基因ε2/ε3基因型[OR(95%CI)=1.763(1.167~2.661)]和ε2等位基因[OR(95%CI)=1.630(1.097~2.421)]是肺结核患病的危险因素。结论: 携带ApoE基因ε2/ε3基因型可能降低肺结核患者的血脂水平;携带ApoE基因ε2/ε3基因型和ε2等位基因人群肺结核患病风险更大。

关键词: 结核,肺, 载脂蛋白E类, 基因, 多态性,单核苷酸, 血脂异常

Abstract:

Objective: To explore the correlation between apolipoprotein E (ApoE) gene polymorphism and blood lipid levels with pulmonary tuberculosis. Methods: A retrospective study was conducted in 1118 patients diagnosed with pulmonary tuberculosis in Meizhou People’s Hospital from January 1, 2016 to December 12, 2020 (case group), and 582 healthy people in the hospital during the same period were selected as the control group. The general information (age, sex) and laboratory test indicators (blood routine test, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and ApoE genotyping test results) of the subjects were collected. The distribution of ApoE genotypes, differences in blood lipid levels, and the correlation between ApoE genotypes and blood lipid levels between the case group and the control group were analyzed, and multivariate logistic regression was used to analyze the impact of ApoE genotypes and blood lipid levels on the incidence of pulmonary tuberculosis. Results: The levels of TG, TC, HDL-C, LDL-C, Apo-A1, and Apo-B in the case group were 1.23 (0.76, 1.47) mmol/L, (4.18±1.17) mmol/L, (1.14±0.38) mmol/L, (2.36±0.82) mmol/L, (0.94±0.32) g/L, and (0.79±0.26) g/L, respectively, and were all lower than those in the control group (1.64 (1.07, 2.06) mmol/L, (5.24±1.18) mmol/L, (1.36±0.34) mmol/L, (2.98±0.90) mmol/L, (1.31±0.33) g/L, (0.97±0.29) g/L, respectively), and the differences were statistically significant (U=-12.603, t=17.605, t=12.096, t=13.784, t=22.614, t=12.071, all P values <0.001). The TG, TC, HDL-C, LDL-C, Apo-A1, and Apo-B levels of individuals carrying the ApoE ε2/ε3 genotype in the case group were 1.21 (0.73, 1.38) mmol/L, (3.81±1.21) mmol/L, (1.17±0.36) mmol/L, (2.01±0.79) mmol/L, (0.96±0.32) g/L, and (0.67±0.22) g/L, respectively, lower than those in the control group (1.56 (0.96, 1.95) mmol/L, (4.78±1.03) mmol/L, (1.42±0.39) mmol/L, (2.50±0.81) mmol/L, (1.39±0.36) g/L, (0.83±0.28) g/L, respectively), and the differences were statistically significant (U=-3.805, t=5.009, t=3.968, t=3.666, t=7.755, t=3.491, all P values <0.001). The levels of TC, LDL-C, and Apo-B in patients carrying the ApoE ε2/ε3 genotype in the case group were (3.81±1.21) mmol/L, (2.01±0.79) mmol/L, and (0.67±0.22) g/L, respectively, which were lower than those carrying the ApoE ε3/ε3 genotype ((4.21±1.09) mmol/L, (2.40±0.76) mmol/L, and (0.81±0.25) g/L, respectively), with statistically significant differences (t values were 0.471, 5.595, and 5.681, respectively, all P values <0.001). The genotype frequency of ApoE ε2/ε3 genotype in the case group was 13.1% (146/1118),which was significantly higher than that in the control group (8.4% (49/582); χ²=8.114, P=0.004). ε2 allele frequency in the case group (7.7% (174/2236)) was significantly higher than that of the control group (5.8% (67/1164); χ²=4.770, P=0.029). Multivariate logistic regression analysis showed that carrying the ApoE ε2/ε3 genotypes (OR (95%CI)=1.763 (1.167-2.661))and ε2 allele gene (OR (95%CI)=1.630 (1.097-2.421)) were risk factors for pulmonary tuberculosis. Conclusion: Carrying ApoE ε2/ε3 genotype may lower the blood lipid levels in pulmonary tuberculosis patients, and carrying ApoE ε2/ε3 genotypes and ε2 allele population has a higher risk of developing pulmonary tuberculosis.

Key words: Tuberculosis, pulmonary, Apolipoproteins E, Genes, Polymorphism, single nucleotide, Dyslipidemias

中图分类号:

R521

余志康, 熊娜婷, 吴和明, 杜京津, 李凌. 载脂蛋白E基因多态性及血脂水平与肺结核易感性分析[J]. 中国防痨杂志, 2023, 45(8): 752-760. doi: 10.19982/j.issn.1000-6621.20230111

Yu Zhikang, Xiong Nating, Wu Heming, Du Jingjin, Li Ling. Analysis of correlation between apolipoprotein E gene polymorphisms and lipid levels with susceptibility to pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2023, 45(8): 752-760. doi: 10.19982/j.issn.1000-6621.20230111

图/表 5

表1

不同临床特征在对照组和病例组中分布情况的比较

特征	对照组(582名)	病例组(1118例)	统计检验值	P值
年龄(岁, $x ˉ$ ±s)	60.15±11.98	61.97±15.34	t=-2.690	0.013
年龄组[名/例(构成比,%)]			χ²=25.881	<0.001
>65岁	190(32.6)	508(45.4)
≤65岁	392(67.4)	610(54.6)
性别[名/例(构成比,%)]			χ²=118.67	<0.001
男性	363(62.4)	955(85.4)
女性	219(37.6)	163(14.6)
甘油三酯[mmol/L,M(Q₁,Q₃)]	1.64(1.07,2.06)	1.23(0.76,1.47)	U=-12.603	<0.001
甘油三酯分组[名/例(构成比,%)]^a			χ²=28.000	<0.001
≤1.7mmol/L	418(71.8)	926(82.8)
>1.7mmol/L	164(28.2)	192(17.2)
总胆固醇(mmol/L, $x ˉ$ ±s)	5.24±1.18	4.18±1.17	t=17.605	<0.001
总胆固醇分组[名/例(构成比,%)]^a			χ²=43.871	<0.001
≤5.2mmol/L	407(69.9)	936(83.7)
>5.2mmol/L	175(30.1)	182(16.3)
高密度脂蛋白胆固醇(mmol/L, $x ˉ$ ±s)	1.36±0.34	1.14±0.38	t=12.096	<0.001
高密度脂蛋白胆固醇分组[名/例(构成比,%)]^a			χ²=8.865	0.003
≤2.0mmol/L	552(94.8)	1091(97.6)
>2.0mmol/L	30(5.2)	27(2.4)
低密度脂蛋白胆固醇(mmol/L, $x ˉ$ ±s)	2.98±0.90	2.36±0.82	t=13.784	<0.001
低密度脂蛋白胆固醇分组[名/例(构成比,%)]^a			χ²=97.426	<0.001
≤3.367mmol/L	400(68.7)	987(88.3)
>3.367mmol/L	182(31.3)	131(11.7)
载脂蛋白A1(g/L, $x ˉ$ ±s)	1.31±0.33	0.94±0.32	t=22.614	<0.001
载脂蛋白A1分组[名/例(构成比,%)]^a			χ²=49.011	<0.001
≤1.16g/L	385(66.2)	910(81.4)
>1.16g/L	197(33.8)	208(18.6)
载脂蛋白B(g/L, $x ˉ$ ±s)	0.97±0.29	0.79±0.26	t=12.071	<0.001
载脂蛋白B分组[名/例(构成比,%)]^a			χ²=73.188	<0.001
≤1.11g/L	431(74.1)	1005(89.9)
>1.11g/L	151(25.9)	113(10.1)
白细胞计数[×10⁹/L,M(Q₁,Q₃)]	7.49(6.10,8.70)	9.73(6.60,11.50)	U=-9.636	<0.001
中性粒细胞绝对值[×10⁹/L,M(Q₁,Q₃)]	4.41(3.30,5.20)	7.45(4.40,9.25)	U=-16.820	<0.001
淋巴细胞绝对值[×10⁹/L,M(Q₁,Q₃)]	2.34(1.80,2.7)	1.41(0.90,1.80)	U=-23.428	<0.001
单核细胞绝对值[×10⁹/L,M(Q₁,Q₃)]	0.53(0.40,0.60)	0.70(0.50,0.90)	U=-9.274	<0.001
血小板计数[×10⁹/L,M(Q₁,Q₃)]	240.31(193.00,276.00)	272.10(190.00,334.25)	U=-4.513	<0.001
红细胞计数(×10¹²/L, $x ˉ$ ±s)	4.91±0.66	4.35±0.85	t=14.833	<0.001
血红蛋白(g/L, $x ˉ$ ±s)	143.50±17.34	123.14±24.41	t=19.739	<0.001

表1

表2

表3

各血脂指标水平在携带不同载脂蛋白E基因型者中的分布情况

血脂水平	ε2/ε2	ε2/ε3	ε2/ε4	ε3/ε3	ε3/ε4	ε4/ε4
甘油三酯(mmol/L)
对照组	1.69(0.88,2.38)	1.56(0.96,1.95)	1.31(0.66,1.97)	1.64(1.08,2.09)	1.69(1.06,2.10)	1.90(1.27,1.575)
病例组	1.59(0.63,2.46)	1.21(0.73,1.38)	0.88(0.48,0.81)	1.21(0.78,1.47)	1.23(0.77,1.49)	3.58(1.03,1.32)
总胆固醇(mmol/L)
对照组	4.48(2.74,5.45)	4.78±1.03	4.89±1.21	5.30±1.20	5.27±1.08	5.13(4.23,5.61)
病例组	3.30(2.38,3.62)	3.81±1.21	4.14±1.20	4.21±1.09	4.35±1.26	4.93(2.68,4.35)
高密度脂蛋白胆固醇(mmol/L)
对照组	1.36±0.21	1.42±0.39	1.44±0.25	1.35±0.33	1.37±0.37	1.21(1.14,1.33)
病例组	1.185±0.45	1.17±0.36	1.37±0.36	1.14±0.38	1.13±0.34	0.88(0.59,1.18)
低密度脂蛋白胆固醇(mmol/L)
对照组	1.96(0.74,3.27)	2.50±0.81	2.81±1.05	3.044±0.88	2.99±0.89	2.86(2.19,3.48)
病例组	1.034(0.95,1.14)	2.01±0.79	2.28±0.85	2.40±0.76	2.53±0.91	2.43(1.49,3.60)
载脂蛋白A1(g/L)
对照组	1.20±0.23	1.39±0.36	1.34±0.18	1.30±0.30	1.33±0.41	1.13(1.03,1.24)
病例组	1.04±0.37	0.96±0.32	1.03±0.28	0.94±0.33	0.93±0.28	0.85(0.49,1.06)
载脂蛋白B(g/L)
对照组	0.63(0.30,1.03)	0.83±0.28	0.89±0.31	0.98±0.28	0.98±0.31	0.93(0.81,0.97)
病例组	0.43(0.33,0.55)	0.67±0.22	0.76±0.25	0.81±0.25	0.83±0.26	0.71(0.45,0.94)
统计检验值	U=-0.183	U=-3.805	U=-1.440	U=-10.587	U=-5.188	U=-1.051
P值^a	0.855	<0.001	0.150	<0.001	<0.001	0.293
统计检验值	U=-1.278	t=5.009	t=1.429	t=15.420	t=4.33	U=-0.945
P值^b	0.201	<0.001	0.177	<0.001	<0.001	0.345
统计检验值	t=0.815	t=3.968	t=0.461	t=9.707	t=5.954	U=-1.997
P值^c	0.436	<0.001	0.649	<0.001	<0.001	0.046
统计检验值	U=-0.730	t=3.666	t=1.292	t=12.515	t=4.043	U=-0.946
P值^d	0.273	<0.001	0.210	<0.001	<0.001	0.344
统计检验值	t=0.864	t=7.755	t=2.855	t=18.851	t=9.567	U=-1.787
P值^e	0.410	<0.001	0.009	<0.001	<0.001	0.074
统计检验值	U=-0.274	t=3.491	t=1.080	t=10.905	t=4.043	U=-1.524
P值^f	0.784	0.001	0.292	<0.001	<0.001	0.128

表3

表4

表5

肺结核患病影响因素的多因素logistic回归分析

变量	β值	s $x ˉ$ 值	Wald χ²值	P值	OR(95%CI)值
年龄>65岁	0.478	0.129	13.703	0.001	1.613(1.252~2.077)
男性	0.698	0.146	22.831	0.001	2.009(1.509~2.674)
甘油三酯>1.7mmol/L	-0.945	0.145	42.749	0.001	0.389(0.293~0.516)
总胆固醇>5.2mmol/L	-0.781	0.191	16.752	0.001	0.458(0.315~0.666)
高密度脂蛋白胆固醇>2.0mmol/L	0.67	0.309	4.713	0.030	1.955(1.067~3.581)
低密度脂蛋白胆固>3.367mmol/L	-0.141	0.235	0.36	0.548	0.869(0.548~1.376)
载脂蛋白A1>1.16g/L	-1.952	0.134	213.75	0.001	0.142(0.109~0.184)
载脂蛋白B>1.11g/L	0.093	0.228	0.167	0.683	1.098(0.703~1.715)
载脂蛋白E基因型
ε2/ε2	-0.468	0.677	0.478	0.489	0.626(0.166~2.360)
ε2/ε3	0.567	0.210	7.266	0.007	1.763(1.167~2.661)
ε2/ε4	0.121	0.539	0.050	0.823	1.128(0.392~3.245)
ε3/ε4	-0.035	0.170	0.043	0.835	0.965(0.692~1.346)
ε4/ε4	-0.489	0.600	0.666	0.414	0.613(0.189~1.986)
等位基因
ε2	0.489	0.202	5.859	0.015	1.630(1.097~2.421)
ε4	-0.066	0.165	0.159	0.691	0.937(0.678~1.293)

表5

参考文献 29

[1]	Cadena AM, Fortune SM, Flynn JL. Heterogeneity in tuberculosis. Nat Rev Immunol, 2017, 17(11): 691-702. doi:10.1038/nri.2017.69. doi: 10.1038/nri.2017.69 pmid: 28736436
[2]	Cai L, Li Z, Guan X, et al. The Research Progress of Host Genes and Tuberculosis Susceptibility. Oxid Med Cell Longev, 2019, 2019: 9273056. doi:10.1155/2019/9273056. doi: 10.1155/2019/9273056
[3]	Maurya RK, Bharti S, Krishnan MY. Triacylglycerols: Fuelling the Hibernating Mycobacterium tuberculosis. Front Cell Infect Microbiol, 2018, 8: 450. doi:10.3389/fcimb.2018.00450. doi: 10.3389/fcimb.2018.00450 URL
[4]	Daniel J, Maamar H, Deb C, et al. Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages. PLoS Pathog, 2011, 7(6): e1002093. doi:10.1371/journal.ppat.1002093. doi: 10.1371/journal.ppat.1002093 URL
[5]	Carlos P, Vargas MH, Torrescruz A, et al. La hipocolesterolemia: un hallazgo frecuente que se asocia a la tuberculosis. Revista Del Instituto Nacional De Enfermedades Respiratorias, 2002, 15(1): 7-11.
[6]	Soh AZ, Chee CB, Wang YT, et al. Dietary Cholesterol Increases the Risk whereas PUFAs Reduce the Risk of Active Tuberculosis in Singapore Chinese. J Nutr, 2016, 146(5): 1093-1100. doi:10.3945/jn.115.228049. doi: 10.3945/jn.115.228049 pmid: 27075903
[7]	Martens GW, Arikan MC, Lee J, et al. Hypercholesterolemia impairs immunity to tuberculosis. Infect Immun, 2008, 76(8): 3464-3472. doi:10.1128/IAI.00037-08. doi: 10.1128/IAI.00037-08 pmid: 18505807
[8]	Deniz O, Gumus S, Yaman H, et al. Serum total cholesterol, HDL-C and LDL-C concentrations significantly correlate with the radiological extent of disease and the degree of smear positivity in patients with pulmonary tuberculosis. Clin Biochem, 2007, 40(3/4): 162-166. doi:10.1016/j.clinbiochem.2006.10.015. doi: 10.1016/j.clinbiochem.2006.10.015 URL
[9]	Lumsden AL, Mulugeta A, Zhou A, et al. Apolipoprotein E (APOE) genotype-associated disease risks: a phenome-wide, registry-based, case-control study utilising the UK Biobank. EBioMedicine, 2020, 59: 102954. doi:10.1016/j.ebiom.2020.102954. doi: 10.1016/j.ebiom.2020.102954
[10]	Kuo CL, Pilling LC, Atkins JL, et al. ApoE e4e 4 Genotype and Mortality With COVID-19 in UK Biobank. J Gerontol A Biol Sci Med Sci, 2020, 75(9): 1801-1803. doi:10.1093/gerona/glaa169. doi: 10.1093/gerona/glaa169 URL
[11]	Wang D, Zhang DF, Li GD, et al. A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China. Br J Dermatol, 2018, 178(4): 931-939. doi:10.1111/bjd.16020. doi: 10.1111/bjd.16020 pmid: 28977675
[12]	Kuhlmann I, Minihane AM, Huebbe P, et al. Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review. Lipids Health Dis, 2010, 9: 8. doi:10.1186/1476-511X-9-8. doi: 10.1186/1476-511X-9-8 pmid: 20109174
[13]	Martin GM. APOE alleles and lipophylic pathogens. Neurobiol Aging, 1999, 20(4):441-443. doi:10.1016/s0197-4580(99)00078-0. doi: 10.1016/s0197-4580(99)00078-0 pmid: 10604437
[14]	Wozniak MA, Maude RJ, Innes JA, et al. Apolipoprotein E-epsilon2 confers risk of pulmonary tuberculosis in women from the Indian subcontinent-a preliminary study. J Infect, 2009, 59(3): 219-222. doi:10.1016/j.jinf.2009.07.003. doi: 10.1016/j.jinf.2009.07.003 URL
[15]	Rao H, Wu H, Yu Z, et al. APOE Genetic Polymorphism rs 7412 T/T Genotype May Be a Risk Factor for Essential Hypertension among Hakka People in Southern China. Int J Hypertens, 2022, 2022: 8145896. doi:10.1155/2022/814589. doi: 10.1155/2022/814589
[16]	Yao X, Gordon EM, Figueroa DM, et al. Emerging Roles of Apolipoprotein E and Apolipoprotein A-I in the Pathogenesis and Treatment of Lung Disease. Am J Respir Cell Mol Biol, 2016, 55(2): 159-169. doi:10.1165/rcmb.2016-0060TR. doi: 10.1165/rcmb.2016-0060TR URL
[17]	van den Elzen P, Garg S, León L, et al. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature, 2005, 437(7060): 906-910. doi:10.1038/nature04001. doi: 10.1038/nature04001
[18]	Figueroa DM, Gordon EM, Yao X, et al. Apolipoproteins as context-dependent regulators of lung inflammation. Mechanisms and Manifestations of Obesity in Lung Disease, 2019:301-326. doi:10.1016/B978-0-12-813553-2.00013-0. doi: 10.1016/B978-0-12-813553-2.00013-0
[19]	Tudorache IF, Trusca VG, Gafencu AV. Apolipoprotein E-A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features. Comput Struct Biotechnol J, 2017, 15: 359-365. doi:10.1016/j.csbj.2017.05.003. doi: 10.1016/j.csbj.2017.05.003 URL
[20]	Mahley RW, Rall SC Jr. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet, 2000, 1:507-537. doi:10.1146/annurev.genom.1.1.507. doi: 10.1146/annurev.genom.1.1.507 pmid: 11701639
[21]	Laval T, Chaumont L, Demangel C. Not too fat to fight: The emerging role of macrophage fatty acid metabolism in immunity to Mycobacterium tuberculosis. Immunol Rev, 2021, 301(1): 84-97. doi:10.1111/imr.12952. doi: 10.1111/imr.12952 URL
[22]	Rosenson RS, Brewer HB Jr, Davidson WS, et al. Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation, 2012, 125(15): 1905-1919. doi:10.1161/CIRCULATIONAHA.111.066589. doi: 10.1161/CIRCULATIONAHA.111.066589 pmid: 22508840
[23]	Chidambaram V, Zhou L, Ruelas Castillo J, et al. Higher Serum Cholesterol Levels Are Associated With Reduced Systemic Inflammation and Mortality During Tuberculosis Treatment Independent of Body Mass Index. Front Cardiovasc Med, 2021, 8: 696517. doi:10.3389/fcvm.2021.696517. doi: 10.3389/fcvm.2021.696517 URL
[24]	Wang J, Yin Y, Wang X, et al. Ratio of monocytes to lymphocytes in peripheral blood in patients diagnosed with active tuberculosis. Braz J Infect Dis, 2015, 19(2):125-131. doi:10.1016/j.bjid.2014.10.008. doi: 10.1016/j.bjid.2014.10.008 pmid: 25529365
[25]	Farivar TN, Moud BS, Sargazi M, et al. Apolipoprotein E Polymorphism in Tuberculosis Patients. Journal of Applied Sciences, 2008, 8: 719-722. doi:10.3923/jas.2008.719.722. doi: 10.3923/jas.2008.719.722 URL
[26]	Caruso C, Ligotti ME, Accardi G, et al. How Important Are Genes to Achieve Longevity? Int J Mol Sci, 2022, 23(10): 5635. doi:10.3390/ijms23105635. doi: 10.3390/ijms23105635 URL
[27]	Kulminski AM, Shu L, Loika Y, et al. APOE region molecular signatures of Alzheimer’s disease across races/ethnicities. Neurobiol Aging, 2020, 87:141.e1-141.e8. doi:10.1016/j.neurobiolaging.2019.11.007. doi: 10.1016/j.neurobiolaging.2019.11.007
[28]	Andersen CJ. Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease. Nutrients, 2018, 10(6): 764. doi:10.3390/nu10060764. doi: 10.3390/nu10060764 URL
[29]	Garcia AR, Finch C, Gatz M, et al. APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population. Elife, 2021, 10: e68231. doi:10.7554/eLife.68231. doi: 10.7554/eLife.68231

基因	对照组 (582名)	病例组 (1118例)	χ²值	P值	对照组男性 (363名)	病例组男性 (955例)	χ²值	P值	对照组女性 (219名)	病例组女性 (163例)	χ²值	P值
基因型[频次(频率,%)]
ε2/ε2	5(0.8)	6(0.5)	0.619	0.640	3(0.8)	6(0.6)	0.152	0.696	2(0.9)	0(0.0)	1.496	0.509
ε2/ε3	49(8.4)	146(13.1)	8.114	0.004	30(8.3)	116(12.1)	4.024	0.045	19(8.7)	30(18.4)	7.910	0.005
ε2/ε4	8(1.4)	16(1.4)	0.009	0.925	4(1.1)	15(1.6)	0.407	0.524	4(1.8)	1(0.6)	1.064	0.302
ε3/ε3	418(71.8)	767(68.6)	1.875	0.171	259(71.3)	650(68.1)	1.328	0.249	159(72.6)	117(71.8)	0.032	0.859
ε3/ε4	94(16.2)	175(15.7)	0.71	0.789	63(17.4)	160(16.8)	0.068	0.795	31(14.2)	15(9.2)	2.164	0.141
ε4/ε4	8(1.4)	8(0.7)	1.783	0.182	4(1.1)	8(0.8)	0.204	0.652	4(1.8)	0(0.0)	3.009	0.139
等位基因[频次(频率,%)]
ε2	67(5.8)	174(7.7)	4.770	0.029	40(5.5)	143(7.5)	3.183	0.074	27(6.2)	31(9.5)	2.981	0.084
ε3	979(84.1)	1855(83.0)	0.724	0.395	611(84.2)	1576(82.5)	1.009	0.315	368(84.0)	279(85.6)	0.353	0.553
ε4	118(10.1)	207(9.3)	0.685	0.408	75(10.3)	191(10.0)	0.063	0.801	43(9.8)	16(4.9)	6.321	0.012

载脂蛋白E基因多态性及血脂水平与肺结核易感性分析

Analysis of correlation between apolipoprotein E gene polymorphisms and lipid levels with susceptibility to pulmonary tuberculosis

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变量	赋值	变量	赋值
肺结核	非肺结核=0,肺结核=1	低密度脂蛋白胆固醇	≤3.367mmol/L=0,>3.367mmol/L=1
年龄	≤65岁=0,>65岁=1	低密度脂蛋白胆固醇	≤3.367mmol/L=0,>3.367mmol/L=1
年龄	≤65岁=0,>65岁=1	载脂蛋白A1	≤1.16g/L=0,>1.16g/L=1
性别	女性=0,男性=1	载脂蛋白A1	≤1.16g/L=0,>1.16g/L=1
性别	女性=0,男性=1	载脂蛋白B	≤1.11g/L=0,>1.11g/L=1
甘油三酯	≤1.7mmol/L=0,>1.7mmol/L=1	载脂蛋白B	≤1.11g/L=0,>1.11g/L=1
甘油三酯	≤1.7mmol/L=0,>1.7mmol/L=1	基因型	ε3/ε3=0,ε2/ε2=1,ε2/ε3=2,ε2/ε4=3, ε3/ε4=4, ε4/ε4=5
总胆固醇	≤5.2mmol/L=0,>5.2mmol/L=1	基因型	ε3/ε3=0,ε2/ε2=1,ε2/ε3=2,ε2/ε4=3, ε3/ε4=4, ε4/ε4=5
高密度脂蛋白胆固醇	≤2.0mmol/L=0,>2.0mmol/L=1	等位基因	ε3=0,ε2=1,ε4=2

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