The relationship between cystatin C gene G73A locus and appolipoprotein E gene polymorphisms and vascular cognitive impairment

doi:10.3877/cma.j.issn.2095-655X.2019.02.004

Abstract

Abstract:

Objective

To investigate the relationship of cystatin C gene (CST3) G73A locus and apolipoprotein E (APOE) gene polymorphisms with vascular cognitive impairment(VCI).

Methods

A case-control study was conducted to collect outpatients and inpatients of Neurology department, and healthy subjects in the same period in Affiliated Hospital of Qingdao University from January to June 2015, including 155 patients with VCI, 210 patients with cerebral infarction (CI) without cognitive impairment and 250 healthy subjects as control group (ND). Polymerase chain reaction/restrictive fragment length polymorphism (PCR/RFLP) was used to detect the polymorphism of CST3 G73A and APOE genes. The chi-square test was used to perform genotype and allele analysis. The effects of these two gene polymorphisms on VCI were analyzed by multivariate Logstic regression which to correct the influencing factors.

Results

No statistical differences were demonstrated in CST3 G73A locus genotype frequencies (χ²=3.95, P=0.14) and allele frequencies (χ²=3.95, P=0.14). Compared with non-carrying type, the risk of developing VCI in APOE ε4/4 gene-carrying type is 4.98 times higher than that of CI group (P<0.01, 95%CI: 1.94-12.80), while 5.68 times higher than that of ND group (P<0.01, 95%CI: 2.22-14.60). After correcting the risk factors of the CST3 gene G73A locus and the APOE gene by multiple Logistic regression, the results showed that when the G73A locus was AA mutant, the risk of VCI in the APOE ε4/4 gene-carrying type was 7.19 times higher than that of the CI group (corrected OR: 6.30, 95%CI: 1.34-29.60, P=0.013), while 8.22 times higher than that of the ND group (OR: 7.26, 95%CI: 1.55-34.10, P=0.008).

Conclusion

The AA gene mutation of G73A locus in CST3 may increase the risk of VCI in APOE ε4/4 gene-carrying type.

Key words: Cystatin C, Apolipoproteins E, Vascular cognitive impairment

Jianwei Liu, Yan Wang. The relationship between cystatin C gene G73A locus and appolipoprotein E gene polymorphisms and vascular cognitive impairment[J]. Chinese Journal of Diagnostics(Electronic Edition), 2019, 07(02): 87-93.

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References 22

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基因	引物(5′-3′)	限制性内切酶	酶切产物
CysC	F：TGGGAGGGACGAGGCGTTCC	Sac Ⅱ	GG：41，51，228 bp；AA：127，191 bp；GA：41，51, 127，191，228 bp
G73A	R：TCCATGGGGCCCACCAG
APOE	F：TCCAAGGAGCTGCAGGCGGCGC	Hin6I	ε4/4：72 bp，48 bp，33 bp；ε3 /4：91，72，48，33 bp；ε3/3 91，48，33 bp
	R：ACAGAATTCGCCCCGGCCTGGTACACTGCCA

基因	引物(5′-3′)	限制性内切酶	酶切产物
CysC	F：TGGGAGGGACGAGGCGTTCC	Sac Ⅱ	GG：41，51，228 bp；AA：127，191 bp；GA：41，51, 127，191，228 bp
G73A	R：TCCATGGGGCCCACCAG
APOE	F：TCCAAGGAGCTGCAGGCGGCGC	Hin6I	ε4/4：72 bp，48 bp，33 bp；ε3 /4：91，72，48，33 bp；ε3/3 91，48，33 bp
	R：ACAGAATTCGCCCCGGCCTGGTACACTGCCA

项目	VCI组(n＝155)	CI组(n＝210)	对照组(n＝250)	统计量	P值
年龄(岁，±s)	64.62±0.22	63.87±0.26	64.09±0.28	F＝1.81	0.176
性别(男，例，%)	80(51.61)	110(52.38)	130(52.00)	χ²＝0.21	0.989
TG(mmol/l, ±s)	2.12±0.71	2.66±0.69	2.93±0.60	F＝2.26	0.106
TC(mmol/l, ±s)	4.66±0.69	4.75±0.57	4.66±0.55	F＝0.90	0.440
LDL(mmol/l, ±s)	2.93±0.60	2.82±0.63	2.71±0.54	F＝0.97	0.405
HDL(mmol/l, ±s)	1.22±0.50	1.30±0.48	1.32±0.56	F＝2.06	0.129
糖尿病(例，%)	45(29.03)	77(36.67)	52(20.80)	χ²＝5.88	0.169
饮酒史(例，%)	43(27.74)	67(31.90)	41(16.40)	χ²＝14.94	0.001
吸烟史(例，%)	40(25.81)	64(30.48)	53(21.20)	χ²＝3.93	0.141
高血压病(例，%)	51(32.90)	41(19.52)	75(30.00)	χ²＝3.17	0.205

项目	VCI组(n＝155)	CI组(n＝210)	对照组(n＝250)	统计量	P值
年龄(岁，±s)	64.62±0.22	63.87±0.26	64.09±0.28	F＝1.81	0.176
性别(男，例，%)	80(51.61)	110(52.38)	130(52.00)	χ²＝0.21	0.989
TG(mmol/l, ±s)	2.12±0.71	2.66±0.69	2.93±0.60	F＝2.26	0.106
TC(mmol/l, ±s)	4.66±0.69	4.75±0.57	4.66±0.55	F＝0.90	0.440
LDL(mmol/l, ±s)	2.93±0.60	2.82±0.63	2.71±0.54	F＝0.97	0.405
HDL(mmol/l, ±s)	1.22±0.50	1.30±0.48	1.32±0.56	F＝2.06	0.129
糖尿病(例，%)	45(29.03)	77(36.67)	52(20.80)	χ²＝5.88	0.169
饮酒史(例，%)	43(27.74)	67(31.90)	41(16.40)	χ²＝14.94	0.001
吸烟史(例，%)	40(25.81)	64(30.48)	53(21.20)	χ²＝3.93	0.141
高血压病(例，%)	51(32.90)	41(19.52)	75(30.00)	χ²＝3.17	0.205

组别	例数	基因型			χ ²值	P值	等位基因		χ ²值	P值
组别	例数	GG	GA	AA	χ ²值	P值	G	A	χ ²值	P值
VCI组	155	84(54.19)	48(30.97)	23(14.83)	?	?	216(69.67)	94(30.32)	?	?
CI组	210	120(57.14)	69(32.86)	21(10.00)	3.40	0.18	309(73.57)	111(26.43)	3.95	0.14
对照组	250	111(44.40)	116(46.40)	23 (9.20)	?	?	338(67.60)	162(32.40)	?	?

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