MTHFR和PCSK9基因与新疆地区维吾尔族及哈萨克族人群心血管病遗传易感性

崔蕴文; 罗健; 刘成; 孟岩; 赵樱; 张新; 梁杰

doi:10.13201/j.issn.1001-1439.2023.01.007

MTHFR和PCSK9基因与新疆地区维吾尔族及哈萨克族人群心血管病遗传易感性

- 新疆医科大学第一附属医院(乌鲁木齐，830000)
基金项目:
新疆维吾尔自治区自然科学基金(No：2019D01C320)

详细信息

通讯作者: 梁杰，E-mail：liangjie1560@163.com

中图分类号: R587.2

收稿日期: 2022-08-29

刊出日期: 2023-01-13

MTHFR, PCSK9 gene and genetic susceptibility to cardiovascular diseases in Uygur and Kazak populations in Xinjiang

- The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, China

More Information

Corresponding author: LIANG Jie, E-mail: liangjie1560@163.com

Received Date: 29 August 2022

Publish Date: 13 January 2023

摘要

摘要: 目的探讨MTHFR和PCSK9基因与新疆地区维吾尔族及哈萨克族人群心血管病遗传易感性的相关性。方法选取中国新疆维吾尔族和哈萨克族心血管疾病患者各652例，以及民族、年龄、性别和地域匹配的健康体检者各652例，PCR扩增N₅，N₁₀-亚甲基四氢叶酸还原酶(MTHFR)C677T及前蛋白转化酶枯草溶菌素-9(PCSK9)基因rs505151(E670G)和rs11591147(R46L)多态性。结果维吾尔族和哈萨克族群体中，冠心病患者的TT突变频率均显著高于对照组(均P < 0.01)。维吾尔族和哈萨克族群体中PCSK9 E670G AA、AG和GG基因型的频率与对照组相比均差异有统计学意义(均P < 0.05)。哈萨克族群体中，G等位基因频率在冠心病组显著高于对照组(P < 0.05)。结论 MTHFR C677T与PCSK9 E670G基因多态性与新疆地区维吾尔族及哈萨克族人群心血管病发生密切相关。
- 亚甲基四氢叶酸还原酶 /
- 前蛋白转化酶枯草溶菌素-9 /
- 维吾尔族 /
- 哈萨克族 /
- 基因多态性
Abstract: Objective To investigate the correlation between N₅, N₁₀-methylenetetrahydrofolate reductase(MTHFR) and preprotein invertase subtilisin/kexin type 9(PCSK9) genes and genetic susceptibility to cardiovascular diseases in Uygur and Kazak populations in Xinjiang.Methods Six hundred and fifty-two Uygur and 652 Kazakh patients with cardiovascular diseases in Xinjiang, China, and 652 healthy people matched by nationality, age, sex, and region were selected for PCR amplification of MTHFR C677T and PCSK9 rs505151(E670G) and rs11591147(R46 L) polymorphisms.Results In both Uygur and Kazakh populations, the frequency of TT mutation in patients with coronary heart disease was significantly higher than that in controls(both P < 0.01). The frequencies of PCSK9 E670G AA, AG, and GG genotypes in Uygur and Kazakh populations were significantly different from those in controls(all P < 0.05). In the Kazakh population, the frequency of G allele in the coronary heart disease group was significantly higher than that in the control group(P < 0.05).Conclusion MTHFR C677T and PCSK9 E670G gene polymorphisms are closely related to cardiovascular disease occurrence in Uygur and Kazakh populations in Xinjiang.
- methylenetetrahydrofolate reductase /
- preprotein invertase subtilisin/kexin type 9 /
- Uygur /
- Kazakh /
- gene polymorphism

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表 1 引物序列信息

Table 1. Primer sequences

基因位点	上游引物(5’-3’)	下游引物(5’-3’)	退火温度/℃	片段长度/bp
MTHFR C677T	TCCCGCAGACACCTTCTCCTTCA	ACATCTCACCGCACCGTCCT	58	217
PCSK9 E670G	TTGGGACACAACCGTGTATCTC	TTGGGACACAACCGTGTATCTC	60	549
PCSK9 R46L	AGAAGACCTAGAGGCCGTG	TACCGAGGAGGACGGCCT	60	407

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表 2 维吾尔族对照组和冠心病组MTHFR C677T基因多态性

Table 2. MTHFR C677T gene polymorphism in coronary heart disease group and control group in Uygur populations 频数(%)

MTHFR C677T	对照组(652例)	冠心病组(652例)	P
基因型
CC	331(50.77)	333(51.07)	0.770
CT	299(45.86)	251(38.50)	0.117
TT	22(3.37)	68(10.43)	0.003
TT或CT	321(49.23)	289(44.33)	0.660
等位基因
C	961(73.70)	917(70.32)	0.285
T	343(26.30)	387(29.68)	0.285

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表 3 哈萨克族对照组和冠心病组MTHFR C677T基因多态性

Table 3. MTHFR C677T gene polymorphism in coronary heart disease group and control group in Kazak populations 频数(%)

MTHFR C677T	对照组(652例)	冠心病组(652例)	P
基因型
CC	317(48.62)	305(46.78)	0.850
CT	304(46.63)	268(44.17)	0.341
TT	31(4.75)	79(12.12)	0.001
TT或CT	335(51.38)	347(56.29)	0.540
等位基因
C	938(71.90)	878(67.33)	0.317
T	366(28.10)	426(32.67)	0.317

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表 4 冠心病组和对照组PCSK9 E670G基因型和等位基因分布

Table 4. PCSK9 E670G gene polymorphism in coronary heart disease group and control group 频数(%)

组别	基因型			等位基因
组别	AA	AG	GG	A	G
维吾尔族冠心病组(652例)	280(42.94)	310(47.54)	62(9.51)	870(66.72)	434(33.28)
维吾尔族对照组(652例)	352(53.99)	261(40.03)	39(5.98)	965(74.00)	339(26.00)
	χ²=7.491，df=2，P=0.024			χ²=6.867，df=1，P=0.008
哈萨克族组冠心病(652例)	291(44.63)	290(44.48)	71(10.89)	872(66.87)	432(33.13)
哈萨克族对照组(652例)	364(55.83)	257(39.42)	31(4.75)	985(75.54)	319(24.46)
	χ²=8.211，df=2，P=0.005			χ²=5.053，df=1，P=0.010
注：对照组中PCSK9 E670G基因型的分布处于Hardy-Weinberg平衡(χ²=1.277，P=0.25)。

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表 5 PCSK9 E670G变异基因型的风险估计

Table 5. Risk estimation of PCSK9 E670G variant genotypes

民族	基因型	病例组/例	对照组/例	OR	P	校正OR^a)	P
维吾尔族(652例)	AA	280	352	1.00		1.00
	AG	310	261	1.59(1.01~3.06)	0.031	1.48(0.89~3.04)	0.034
	GG	62	39	2.57(1.08~5.22)	0.018	3.25(1.27~5.84)	0.008
	AG+GG	372	300	1.28(1.01~2.41)	0.042	1.92(1.03~3.11)	0.028
哈萨克族(652例)	AA	291	364	1.00		1.00
	AG	290	257	1.49(1.00~2.18)	0.039	1.46(0.99~2.17)	0.057
	GG	71	31	2.39(1.08~5.22)	0.023	3.01(1.18~5.64)	0.011
	AG+GG	361	288	1.58(1.07~2.32)	0.014	1.62(1.05~2.44)	0.016
注：^a)调整年龄、性别、BMI、吸烟状况、高血压、糖尿病、血脂异常。

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表 6 冠心病患者PCSK9 E670G基因型与表型的比较

Table 6. Correlation between PCSK9 E670G genotype and phenotype in patients with coronary heart disease X±S, M(P₂₅, P₇₅)

项目	维吾尔族冠心病组(652例)			哈萨克族冠心病组(652例)
项目	AA	AG+GG	P	AA	AG+GG	P
体重/kg	69.14±11.38	68.24±8.66	0.418	67.27±11.38	67.52±8.66	0.225
BMI/(kg·m^-2)	24.85±3.38	23.38±4.02	0.562	23.56±4.14	23.62±3.76	0.357
TC/(mmol·L^-1)	4.04(3.40，4.54)	4.05(3.50，4.76)	0.239	3.28(2.24，4.67)	3.24(2.25，5.04)	0.153
TG/(mmol·L^-1)	1.50(1.14，2.06)	1.48(1.04，2.26)	0.881	1.49(1.04，3.01)	1.52(1.00，3.02)	0.677
HDL-C/(mmol·L^-1)	1.00(0.84，2.10)	1.00(0.88，1.18)	0.469	1.21(0.92，3.07)	1.54(1.02，3.41)	0.528
LDL-C/(mmol·L^-1)	2.31(1.72，2.80)	2.34(1.87，2.81)	0.310	2.52(1.52，4.09)	1.87(1.05，3.07)	0.229

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表 7 冠心病组和对照组PCSK9 R46L基因型和等位基因分布

Table 7. PCSK9 R46L gene polymorphism in coronary heart disease group and control group 频数(%)

组别	基因型			等位基因
组别	GG	GT	TT	G	T
维吾尔族冠心病组(652例)	421(64.57)	222(33.94)	19(2.91)	1064(81.59)	260(18.40)
维吾尔族对照组(652例)	392(60.12)	226(34.66)	34(5.21)	1010(74.00)	294(26.00)
	χ²=0.446，df=2，P=0.643			χ²=0.451，df=1，P=0.518
哈萨克族冠心病组(652例)	335(51.38)	280(42.94)	37(5.67)	950(72.85)	354(27.14)
哈萨克族对照组(652例)	368(56.44)	253(38.80)	31(4.75)	989(75.84)	315(24.15)
	χ²=0.211，df=2，P=0.854			χ²=0.353，df=1，P=0.437

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表 8 冠心病风险的多元logistic回归分析

Table 8. Risk of coronary heart diseas analyzed by Multivariate logistic regression analysis

变量	维吾尔族冠心病组		哈萨克族冠心病组
变量	OR(95%CI)	P	OR(95%CI)	P
GT+TT	1.02(0.74~1.28)	0.547	1.08(0.78~1.55)	0.245
年龄	1.09(1.01~1.23)	< 0.001	1.65(1.08~2.64)	< 0.001
性别(男)	1.97(1.12~2.24)	0.002	1.43(1.11~3.07)	0.053
BMI	1.05(0.82~1.25)	0.084	2.51(1.28~3.10)	0.039
吸烟	1.97(1.19~4.11)	0.001	1.26(1.01~2.54)	0.001
高血压	2.84(2.02~5.18)	< 0.001	1.08(0.85~1.94)	0.042
糖尿病	1.45(0.95~3.02)	0.082	1.44(0.95~1.84)	0.127
高血脂	1.90(0.88-2.15)	0.114	2.61(0.96-3.51)	0.114

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