新疆地区FGB基因多态性对纤维蛋白原水平及胆囊结石发病的影响

阿丽叶古丽·艾皮热; 皮尔地瓦斯·麦麦提玉素甫; 王俭; 艾克拜尔·艾力; 克力木·阿不都热依木

doi:10.3969/j.issn.1001-5256.2021.09.032

新疆地区FGB基因多态性对纤维蛋白原水平及胆囊结石发病的影响

DOI: 10.3969/j.issn.1001-5256.2021.09.032

a.
新疆维吾尔自治区人民医院普外微创研究所，乌鲁木齐 830001
b.
新疆维吾尔自治区人民医院微创、疝和腹壁外科，乌鲁木齐 830001

基金项目:

新疆维吾尔自治区自然科学基金项目 (2017D01C096)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：阿丽叶古丽·艾皮热、克力木·阿不都热依木负责课题设计，资料分析，撰写论文；皮尔地瓦斯·麦麦提玉素甫、王俭、艾克拜尔·艾力参与收集全血标本及临床数据；阿丽叶古丽·艾皮热负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
克力木·阿不都热依木，klm6075@163.com

中图分类号: R657.42
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出版历程
- 收稿日期: 2021-01-20
- 录用日期: 2021-04-01
- 出版日期: 2021-09-20

Effects of FGB gene polymorphism on fibrinogen level and gallstones incidence in Xinjiang, China

a.
Institute of Minimally Invasive Surgery, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China
b.
Department of Minimally Invasive, Hernia, and Abdominal Wall Surgery, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China

Research funding:

Natural Science Foundation of Xinjiang Uygur Autonomous Region (2017D01C096)

摘要

摘要: 目的探讨纤维蛋白原β链(FGB)基因rs4220、rs1044291位点多态性与血浆纤维蛋白原(Fg)水平及胆囊结石的相关性。方法收集2017年12月—2020年5月在新疆维吾尔自治区人民医院住院治疗及健康体检的维吾尔族、汉族胆囊结石及非胆囊结石患者各150例，采集血液标本，测定血浆Fg水平，并在前期的FGB基因全外显子测序结果的基础上，选择FGB基因rs4220、rs1044291多态位点，采用SNaPshot法进行基因型鉴定。符合正态分布的计量资料2组间比较采用t检验，非正态分布的计量资料2组间比较采用Mann-Whitney U检验，计数资料组间比较采用χ²检验；各变量与胆囊结石的关系采用多因素logistic回归分析。结果在汉族人群中，胆囊结石组血浆Fg水平高于对照组，差异有统计学意义[2.90(2.43~3.49) g/L vs 2.47(2.06~3.02) g/L，Z=-3.62, P＜0.01]，而维吾尔族人群中无差异。FGB基因rs4220、rs1044291位点基因频率在维吾尔族、汉族胆囊结石组与对照组差异均无统计学意义(P值均＞0.05)；在汉族人群中，胆囊结石组rs4220位点GG基因型者血浆Fg水平高于对照组[2.84(2.32~3.61)g/L vs 2.34(2.05~2.75)g/L，Z=-3.04, P＜0.05]，rs1044291位点T基因型携带者Fg水平高于对照组[(3.08±0.75)g/L vs(2.48±0.48)g/L，t=2.80, P＜0.05)]。在维吾尔族人群中，胆囊结石组与对照组间比较，仅有rs4220位点的A基因携带者血浆Fg水平低于对照组[2.84(2.08~3.06)g/L vs 3.10(2.85~3.98)g/L，Z=-2.41, P＜0.05]。但两个民族胆囊结石组、对照组内，各基因型携带者Fg水平差异均无统计学意义(P值均＞0.05)。结论 FGB基因多态性对血浆Fg水平的影响可能与种族有关；FGB基因rs4220、rs1044291位点多态性可能通过调控Fg水平影响新疆人群胆囊结石的发病。
- 胆囊结石病 /
- 纤维蛋白原 /
- 多态现象, 遗传 /
- 新疆[维吾尔自治区]
Abstract: Objective To investigate the association of the polymorphisms of the FGB gene rs4220 and rs1044291 loci with plasma fibrinogen (Fg) level and gallstones in Xinjiang, China. Methods Blood samples were collected from 150 Uygur and Han patients with gallstones and 150 Uygur and Han individuals without gallstones who were hospitalized or underwent physical examination in The People's Hospital of Xinjiang Uygur Autonomous Region from December 2017 to May 2020. Plasma Fg level was measured, and based on the previous results of whole exon sequencing of the FGB gene, the SNaPshot method was used to identify the genotype at rs4220 and rs1044291 loci of the FGB gene. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to investigate the association between each variable and gallstones. Results For the Chinese Han population, the gallstones group had a significantly higher plasma Fg level than the control group [2.90 (2.43-3.49) g/L vs 2.47 (2.06-3.02) g/L, Z=-3.62, P < 0.01), while there was no significant difference in the Uyghur population. There were no significant differences in the frequencies of genotypes and alleles at the rs4220 and rs1044291 loci of the FGB gene between the gallstones group and the control group in both Uyghur and Han populations (all P > 0.05). For the Chinese Han population, the subjects carrying GG genotype at the rs4220 locus in the gallstones group had a significantly higher plasma Fg level than those in the control group [2.84(2.32-3.61) g/L vs 2.34(2.05-2.75) g/L, Z=-3.04, P < 0.05], and the subjects carrying T genotype at the rs1044291 locus had a significantly higher plasma Fg level than those in the control group (3.08±0.75 g/L vs 2.48±0.48 g/L, t=2.80, P < 0.05). For the Uyghur population, only the subjects carrying A genotype at the rs4220 locus in the gallstones group had a significantly lower plasma Fg level than those in the control group [2.84(2.08-3.06) g/L vs 3.10(2.85-3.98) g/L, Z=-2.41, P < 0.05]. There was no significant difference in plasma Fg level between the subjects carrying different genotypes within the gallstones group or the control group for both Uyghur and Han populations (all P > 0.05). Conclusion The influence of FGB gene polymorphism on plasma Fg level may be associated with race, and FGB gene polymorphisms at the rs4220 and rs1044291 loci may be involved in the pathogenesis of gallstones by regulating Fg level in the population in Xinjiang.
- Cholecystolithiasis /
- Fibrinogen /
- Polymorphism, Genetic /
- XINJIANG

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表 1 PCR引物及单碱基延伸引物序列

位点	引物序列	延伸引物序列
rs4220	F-GCAGATACTACTGGGGTGGACA	AAGGGGTCATGGTACTCAATGA
	R-AACTCCTGACCTTGTGACCG
rs1044291	F-GTCCTCCACCCCTAATGTATCA	TTTTTTTTTTTTTTTTTTTTAGGG
	R-CATTCACTGGCTCTGGGTCT	CCTGACCTGTCCTGGAAT

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表 2 研究对象的一般特征

民族	指标	胆囊结石组	对照组	统计值	P值
维吾尔族	例数	97	73
	年龄(岁)	53.00(44.00~65.50)	50.00(39.50~60.50)	Z=-1.61	0.108
	收缩压(mm Hg)	129(121~143)	130(114~145)	Z=-0.33	0.742
	舒张压(mm Hg)	78.28±10.17	76.89±12.31	t=0.78	0.435
	BMI(kg/m²)	27.34(24.68~30.59)	27.82(24.33~32.10)	Z=-0.30	0.765
	游离脂肪酸(mmol/L)	0.34(0.25~0.47)	0.29(0.22~0.43)	Z=-1.33	0.185
	TC(mmol/L)	4.41±0.86	4.63±1.27	t=-0.86	0.394
	TG(mmol/L)	1.49±0.55	1.34±0.63	t=1.03	0.305
	LDL-C(mmol/L)	2.58±0.76	2.69±1.03	t=-0.47	0.639
	HDL-C(mmol/L)	1.10±0.36	1.25±0.38	t=-0.21	0.043
	Fg(g /L)	2.74(2.52~3.18)	2.82(2.22~3.27)	Z=-0.22	0.828
汉族	例数	51	76
	年龄(岁)	58.76±14.28	55.92±16.07	t=1.02	0.309
	收缩压(mm Hg)	131.39±21.25	131.38±18.08	t=0.003	0.998
	舒张压(mm Hg)	74.16±11.83	78.88±10.98	t=-2.15	0.033
	BMI(kg/m²)	25.63(23.18~28.37)	24.70(22.93~28.62)	Z=-0.54	0.592
	游离脂肪酸(mmol/L)	0.41(0.33~0.60)	0.33(0.20~0.49)	Z=-2.60	0.009
	TC(mmol/L)	4.09(3.63~4.57)	4.29(3.86~5.65)	Z=-1.20	0.230
	TG(mmol/L)	1.26(0.92~1.68)	1.36(0.84~2.23)	Z=-0.42	0.673
	LDL-C(mmol/L)	2.39(2.15~2.73)	2.58(2.10~3.20)	Z=-0.56	0.576
	HDL-C (mmol/L)	1.09±0.23	1.12±0.22	t=-0.42	0.680
	Fg(g /L)	2.90(2.43~3.49)	2.47(2.06~3.02)	Z=-3.62	0.000

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表 3 胆囊结石组FGB基因rs4220、rs1044291位点分布频率Hardy-Weinberg平衡检验

组别	位点	基因型	实际频数	理论频数	χ²值	P值
胆囊结石组	rs4220	GG	99	98.3	0.116	0.944
		GA	44	43.7
		AA	4	5.0
	rs1044291	CC	104	102.4	0.224	0.894
		CT	40	36.7
		TT	3	3.9
对照组	rs4220	GG	99	99.7	0.096	0.953
		AG	44	44.3
		AA	6	5.0
	rs1044291	CC	109	106.6	0.253	0.881
		CT	35	38.3
		TT	5	4.1

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表 4 FGB基因rs4220、rs1044291位点基因型分布

民族	位点	基因型/等位基因	胆囊结石组	对照组	χ²值	P值
维吾尔族	rs4220	GG	63(64.9%)	49(67.1%)	0.092	0.955
		GA	31(32.0%)	22(30.1%)
		AA	3(3.1%)	2(2.7%)
		G	157(80.9%)	120(82.2%)	0.088	0.767
		A	37(19.1%)	26(17.8%)
	rs1044291	CC	64(66.0%)	54(74.0%)	1.280	0.527
		CT	30(30.9%)	17(23.3%)
		TT	3(3.1%)	2(2.7%)
		C	158(81.4%)	125(85.6%)	1.040	0.308
		T	36(18.6%)	21(14.4%)
汉族	rs4220	GG	37(72.5%)	50(65.8%)	1.181	0.554
		GA	13(25.5%)	22(28.9%)
		AA	1(2.0%)	4(5.3%)
		G	87(85.3%)	122(80.3%)	1.060	0.303
		A	15(14.7%)	30(19.7%)
	rs1044291	CC	40(80.0%)	55(72.4%)	1.048	0.592
		CT	9(18.0%)	18(23.7%)
		TT	1(2.0%)	3(3.9%)
		C	89(89.0%)	128(11.0%)	1.157	0.282
		T	11(84.2%)	24(15.8%)

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表 5 胆囊结石组与对照组中各基因型与血浆Fg水平的关系

民族	位点	基因型	Fg水平(g/L)
民族	位点	基因型	胆囊结石组	对照组
汉族	rs4220	GG	2.84(2.32~3.61)¹⁾	2.34(2.05~2.75)
		AG+AA	3.10±0.64	2.67±0.66
	rs1044291	CC	2.93(2.35~3.65)	2.89(2.24~3.32)
		CT+TT	3.08±0.75¹⁾	2.48±0.48
维吾尔族	rs4220	GG	2.68(2.35~3.21)	2.58(2.08~3.11)
		AG+AA	2.84(2.08~3.06)¹⁾	3.10(2.85~3.98)
	rs1044291	CC	2.74(2.52~3.21)	2.89(2.24~3.32)
		CT+TT	2.79(2.48~3.09)	2.80(2.22~3.11)
注：与对照组比较，1)P < 0.05。

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表 6 影响胆囊结石的危险因素分析

自变量	B值	SE	P值	OR	95%CI
族别	0.590	0.241	0.014	1.804	1.125~2.893
Fg	0.052	0.025	0.042	1.053	1.002~1.107

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