微小RNA-143/145基因多态性与冠心病危险因素及严重程度的相关性

doi:10.3881/j.issn.1000-503X.10081

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2018, Vol. 40 ›› Issue (4): 510-518.doi: 10.3881/j.issn.1000-503X.10081

• Original Articles • Previous Articles Next Articles

Associations of the MicroRNA-143/145 Polymorphisms with Cardiovascular Risk Factors and the Severity of Coronary Heart Disease

CHEN Yun¹, LUO Zhi¹, ZENG Wei¹, LAI Feiya², CHEN Qiuhong², Lü Zhan¹(), SONG Yongyan³()

¹Department of Cardiology,Affiliated Hospital,College of Preclinical Medicine,North Sichuan Medical College,Nanchong,Sichuan 637000,China
²School of Clinical Medicine,College of Preclinical Medicine,North Sichuan Medical College,Nanchong,Sichuan 637000,China
³Department of Biochemistry,College of Preclinical Medicine,North Sichuan Medical College,Nanchong,Sichuan 637000,China

Received:2017-10-09 Online:2018-08-30 Published:2018-09-08
Supported by:
Supported by the Key Project of Education Department of Sichuan Province(17ZA0172) and the Cooperative Project on Scientific Research between Nanchong City and North Sichuan Medical College(NSMC20170403)

Abstract

Abstract:

Objective To explore the possible effects of the microRNA(miR)-143/145 polymorphisms on cardiovascular risk factors and the severity of coronary heart disease(CHD) in Chinese Han people. Methods Polymerase chain reaction-restriction fragment length polymorphism analysis was employed to identify the genotypes of the rs353292 and rs4705343 polymorphisms for 380 patients with CHD and 163 CHD-free controls. The physiological and biochemical parameters between the genotypes were compared in the CHD patients and in controls,and the incidence of myocardial infarction(MI) was also compared between the genotypes in the CHD patients. Results The subjects with the rs353292 TT genotype had higher serum levels of triglycerides(F=3.00,P=0.05) and glucose(F=9.91,P<0.001) than the C carriers,and the subjects with the rs4705343 TT genotype had significantly higher prevalence of hypertension(χ²=6.35,P=0.04) than the C carriers in the control group. The patients with the rs353292 TT genotype had significantly higher serum levels of hypersensitive C-reactive protein(hs-CRP)(F=8.43,P<0.001) than the C carriers in the CHD group,and the frequency of MI was significantly higher in the patients with the rs353292 TT genotype than that in the C carrier patients(χ²=5.29,P=0.02). Conclusion The T allele of the rs353292 polymorphism is associated with serum hs-CRP levels in CHD patients,and it may affect the occurrence and development of MI by up-regulation of CRP gene through miR-143/145. The rs4705343 polymorphism is not related to the risk and severity of CHD.

Key words: miR-143/145, rs353292, rs4705343, coronary heart disease, hypersensitive C-reactive protein

CLC Number:

R543.3

CHEN Yun, LUO Zhi, ZENG Wei, LAI Feiya, CHEN Qiuhong, Lü Zhan, SONG Yongyan. Associations of the MicroRNA-143/145 Polymorphisms with Cardiovascular Risk Factors and the Severity of Coronary Heart Disease[J].Acta Academiae Medicinae Sinica, 2018, 40(4): 510-518.

Figures/Tables 6

Table 1

Clinical characteristics of the study population"

分组 Group	年龄( $x ?$ ±s,岁) Age( $x ?$ ±s,years)	体质量 Body mass ( $x ?$ ±s,kg)		体质量指数 Body mass index ( $x ?$ ±s,kg/m²)		高血压 Hypertension [n(%)]		糖尿病 Diabetes [n(%)]		三酰甘油 Triglycerides ( $x ?$ ±s,mmol/L)
对照组Control group(n=163)	59.17±11.60	63.07±10.36		24.05±3.46		62(38.0)		14( 8.6)		1.36±0.68
CHD组CHD group(n=380)	64.12± 9.06	63.22± 9.37		24.17±3.26		208(54.7)		59(15.5)		1.65±1.25
F/χ²	28.54	0.02		0.13		12.72		4.71		7.41
P	<0.001	0.88		0.72		<0.001		0.03		0.01
分组 Group	总胆固醇 Total cholesterol ( $x ?$ ±s,mmol/L)	LDL-C ( $x ?$ ±s,mmol/L)		VLDL-C ( $x ?$ ±s,mmol/L)		HDL-C ( $x ?$ ±s,mmol/L)		载脂蛋白AI Apolipoprotein AI ( $x ?$ ±s,g/L)		载脂蛋白B100 Apolipoprotein B100 ( $x ?$ ±s,g/L)
对照组Control group(n=163)	4.00±1.03	2.51±1.45		0.54±0.26		1.07±0.28		1.11±0.18		0.74±0.24
CHD组CHD group(n=380)	4.22±1.18	2.65±0.93		0.58±0.38		1.00±0.25		1.05±0.20		0.81±0.28
F/χ²	4.00	1.67		1.41		8.39		9.76		7.70
P	0.05	0.20		0.24		<0.01		<0.01		<0.01
分组 Group	脂蛋白(a) Lipoprotein(a) ( $x ?$ ±s,mg/L)		血糖 Blood glucose ( $x ?$ ±s,mmol/L)		hs-CRP ( $x ?$ ±s,mg/L)		尿酸 Uric acid ( $x ?$ ±s,μmol/L)		同型半胱氨酸 Homocysteine ( $x ?$ ±s,μmol/L)
对照组Control group(n=163)	254.36±288.67		5.70±2.06		5.04±11.61		347.40±117.86		13.98±5.91
CHD组CHD group(n=380)	319.69±336.18		6.15±2.36		10.53±20.95		354.79±112.05		14.23±5.06
F/χ²	4.29		4.14		9.11		0.46		0.22
P	0.04		0.04		<0.01		0.50		0.64

Table 1

Fig 1

Table 2

Table 3

Physiological and biochemical parameters of the subjects according to the rs353292 genotypes"

分组 Group	年龄( $x ?$ ±s,岁) Age( $x ?$ ±s,years)	体质量 Body mass ( $x ?$ ±s,kg)		体质量指数 Body mass index ( $x ?$ ±s,kg/m²)		高血压 Hypertension [n(%)]		糖尿病 Diabetes [n(%)]		三酰甘油 Triglycerides ( $x ?$ ±s,mmol/L)
对照组Control group
CC基因型CC genotype(n=110)	58.84±11.87	63.27±10.44		24.01±3.51		43(39.1)		7( 6.4)		1.30±0.60
CT基因型CT genotype(n=39)	61.54±10.64	61.87± 9.82		24.08±3.32		16(41.0)		4(10.3)		1.36±0.67
TT基因型TT genotype(n=14)	55.21±11.42	65.00±11.63		24.29±3.77		3(21.4)		3(21.4)		1.78±1.07^ab
F/χ²	1.69	0.50		0.03		1.84		3.04		3.00
P	0.19	0.61		0.97		0.40		0.22		0.05
CHD组CHD group
CC基因型CC genotype(n=264)	64.55± 8.62	63.32± 9.39		24.31±3.45		143(54.2)		43(16.3)		1.65±1.30
CT基因型CT genotype(n=86)	63.52± 9.67	62.36± 8.43		23.65±2.52		48(55.8)		11(12.8)		1.68±1.22
TT基因型TT genotype(n=30)	62.10±10.84	65.14±11.88		24.51±3.48		17(56.7)		5(16.7)		1.49±0.77
F/χ²	1.23	0.90		1.41		0.12		0.66		0.25
P	0.29	0.41		0.25		0.94		0.72		0.78
分组 Group	总胆固醇 Total cholesterol ( $x ?$ ±s,mmol/L)	LDL-C ( $x ?$ ±s,mmol/L)		VLDL-C ( $x ?$ ±s,mmol/L)		HDL-C ( $x ?$ ±s,mmol/L)		载脂蛋白AI Apolipoprotein AI ( $x ?$ ±s,g/L)		载脂蛋白B100 Apolipoprotein B100 ( $x ?$ ±s,g/L)
对照组Control group
CC基因型CC genotype(n=110)	4.00±1.01	2.59±1.67		0.54±0.26		1.05±0.26		1.10±0.16		0.75±0.24
CT基因型CT genotype(n=39)	4.03±1.05	2.40±0.81		0.50±0.25		1.13±0.30		1.15±0.19		0.73±0.22
TT基因型TT genotype(n=14)	3.89±1.14	2.24±0.75		0.65±0.32		1.00±0.37		1.06±0.25		0.73±0.22
F/χ²	0.10	0.47		1.55		1.51		1.76		0.12
P	0.91	0.63		0.22		0.22		0.18		0.89
CHD组CHD group
CC基因型CC genotype(n=264)	4.25±1.22	2.68±0.95		0.59±0.39		1.00±0.25		1.05±0.20		0.82±0.28
CT基因型CT genotype(n=86)	4.15±1.09	2.57±0.84		0.56±0.38		1.00±0.24		1.06±0.16		0.77±0.26
TT基因型TT genotype(n=30)	4.15±1.02	2.65±0.95		0.54±0.34		0.96±0.22		1.00±0.20		0.83±0.28
F/χ²	0.28	0.49		0.27		0.31		1.08		1.27
P	0.76	0.61		0.76		0.73		0.34		0.28
分组 Group	脂蛋白(a) Lipoprotein(a) ( $x ?$ ±s,mg/L)		血糖 Blood glucose ( $x ?$ ±s,mmol/L)		hs-CRP ( $x ?$ ±s,mg/L)		尿酸 Uric acid ( $x ?$ ±s,μmol/L)		同型半胱氨酸 Homocysteine ( $x ?$ ±s,μmol/L)
对照组Control group
CC基因型CC genotype(n=110)	241.64±283.48		5.50±1.45		6.10±13.85		345.93±115.24		14.43±6.63
CT基因型CT genotype(n=39)	318.61±333.96		5.45±1.10		2.13±1.69		342.87±123.83		12.92±4.16
TT基因型TT genotype(n=14)	179.23±149.59		7.92±4.99^ab		4.91±6.06		371.45±129.31		13.37±3.29
F/χ²	1.41		9.91		1.56		0.30		0.92
P	0.25		<0.001		0.21		0.74		0.40
CHD组CHD group
CC基因型CC genotype(n=264)	308.47±324.66		6.20±2.44		9.70±19.64		352.56±108.66		14.54±5.54
CT基因型CT genotype(n=86)	358.15±382.05		5.86±2.09		8.26±17.61		365.19±114.15		13.76±3.68
TT基因型TT genotype(n=30)	305.85±287.27		6.48±2.34		26.66±34.48^ab		344.64±136.90		12.51±3.16
F/χ²	0.70		0.95		8.43		0.52		2.24
P	0.50		0.39		<0.001		0.60		0.11

Table 3

Table 4

Physiological and biochemical parameters of the subjects according to the rs4705343 genotypes"

分组 Group	年龄( $x ?$ ±s,岁) Age( $x ?$ ±s,years)	体质量 Body mass ( $x ?$ ±s,kg)		体质量指数 Body mass index ( $x ?$ ±s,kg/m²)		高血压 Hypertension [n(%)]		糖尿病 Diabetes [n(%)]		三酰甘油 Triglycerides ( $x ?$ ±s,mmol/L)
对照组Control group
TT基因型TT genotype(n=56)	59.14±10.94	63.79±10.13		24.36±2.79		28(50.0)		6(10.7)		1.45±0.70
CT基因型CT genotype(n=89)	59.26±11.74	63.13±10.80		24.06±3.84		26(29.2)^a		8(9.0)		1.32±0.65
CC基因型CC genotype(n=6)	57.00±3.52	63.40±10.57		25.49±3.91		2(33.3)		0		1.46±0.86
F/χ²	0.11	0.06		0.45		6.35		1.31		0.60
P	0.89	0.94		0.64		0.04		0.52		0.55
CHD组CHD group
TT基因型TT genotype(n=113)	64.37±8.33	62.46±9.67		24.18±3.28		57(50.4)		16(14.2)		1.56±0.99
CT基因型CT genotype(n=205)	63.90±9.48	64.48±9.11		24.50±3.26		120(58.5)		35(17.1)		1.66±1.05
CC基因型CC genotype(n=11)	64.00±11.33	60.10±8.94		23.18±2.87		8(72.7)		2(18.2)		2.07±1.45
F/χ²	0.09	2.36		0.98		3.25		0.50		1.14
P	0.91	0.10		0.38		0.20		0.78		0.32
分组 Group	总胆固醇 Total cholesterol ( $x ?$ ±s,mmol/L)	LDL-C ( $x ?$ ±s,mmol/L)		VLDL-C ( $x ?$ ±s,mmol/L)		HDL-C ( $x ?$ ±s,mmol/L)		载脂蛋白AI Apolipoprotein AI ( $x ?$ ±s,g/L)		载脂蛋白B100 Apolipoprotein B100 ( $x ?$ ±s,g/L)
对照组Control group
TT基因型TT genotype(n=56)	3.96±1.04	2.37±0.83		0.57±0.28		1.02±0.22		1.10±0.17		0.73±0.23
CT基因型CT genotype(n=89)	4.08±1.07	2.66±1.81		0.53±0.26		1.11±0.32		1.12±0.19		0.76±0.25
CC基因型CC genotype(n=6)	4.18±0.74	2.50±0.64		0.62±0.22		1.05±0.28		1.11±0.10		0.80±0.15
F/χ²	0.25	0.58		0.65		1.54		0.23		0.41
P	0.78	0.56		0.52		0.22		0.79		0.67
CHD组CHD group
TT基因型TT genotype(n=113)	4.29±1.06	2.71±0.88		0.60±0.39		1.03±0.25		1.07±0.19		0.84±0.29
CT基因型CT genotype(n=205)	4.19±1.15	2.64±0.92		0.57±0.35		0.96±0.25		1.03±0.20		0.82±0.28
CC基因型CC genotype(n=11)	4.12±0.88	2.36±0.63		0.73±0.54		1.03±0.23		1.09±0.14		0.81±0.29
F/χ²	0.34	0.77		0.83		2.45		1.74		0.28
P	0.71	0.47		0.44		0.09		0.18		0.76
分组 Group	脂蛋白(a) Lipoprotein(a) ( $x ?$ ±s,mg/L)		血糖 Blood glucose ( $x ?$ ±s,mmol/L)		hs-CRP ( $x ?$ ±s,mg/L)		尿酸 Uric acid ( $x ?$ ±s,μmol/L)		同型半胱氨酸 Homocysteine ( $x ?$ ±s,μmol/L)
对照组Control group
TT基因型TT genotype(n=56)	297.42±321.02		5.68±1.32		3.83±4.72		337.09±124.54		14.04±4.12
CT基因型CT genotype(n=89)	239.76±275.18		5.83±2.47		5.50±13.10		357.83±112.27		13.90±6.98
CC基因型CC genotype(n=6)	180.57±217.01		6.25±1.56		3.50±2.10		348.70±75.81		13.29±1.76
F/χ²	0.83		0.23		0.44		0.51		0.04
P	0.44		0.80		0.64		0.60		0.96
CHD组CHD group
TT基因型TT genotype(n=113)	311.83±321.90		6.06±2.21		9.80±19.70		336.45±101.88		14.22±5.24
CT基因型CT genotype(n=205)	342.60±350.51		6.38±2.50		12.09±23.49		367.80±121.22		14.32±5.24
CC基因型CC genotype(n=11)	211.17±352.15		5.69±1.37		11.71±21.97		342.12±42.54		16.11±6.94
F/χ²	0.77		0.89		0.38		2.80		0.48
P	0.46		0.41		0.69		0.06		0.62

Table 4

Fig 2

References 20

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Associations of the MicroRNA-143/145 Polymorphisms with Cardiovascular Risk Factors and the Severity of Coronary Heart Disease

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分组 Group	rs353292
分组 Group	CC基因型 CC genotype[n(%)]	CT基因型 CT genotype[n(%)]	TT基因型 TT genotype [n(%)]	C等位基因频率 C allele frequency	T等位基因频率 T allele frequency
对照组Control group(n=163)	110(67.5)	39(23.9)	14(8.6)	0.79	0.21
CHD组CHD group(n=380)	264(69.5)	86(22.6)	30(7.9)	0.81	0.19
χ²	0.22			0.26
P	0.90			0.61
分组 Group	rs4705343
分组 Group	TT基因型 TT genotype[n(%)]	CT基因型 CT genotype[n(%)]	CC基因型 CC genotype[n(%)]	T等位基因频率 T allele frequency	C等位基因频率 C allele frequency
对照组Control group(n=163)	56(37.1)	89(58.9)	6(4.0)	0.67	0.33
CHD组CHD group(n=380)	113(34.3)	205(62.3)	11(3.3)	0.66	0.34
χ²	0.53			0.10
P	0.77			0.75

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