Association study between microRNA-938 and TGFBR1 single nucleotide polymorphisms and hemorrhagic stroke

doi:10.3877/cma.j.issn.2095-123X.2019.04.004

Abstract

Abstract:

Objective

To investigate the association between rs12346650 G>A polymorphisms in transforming growth factor β receptor 1 (TGFBR1) gene and rs2505901 C>T polymorphisms in microRNA-938 and hemorrhagic stroke (HS).

Methods

A total of 239 patients with acute HS and 993 controls from a community population were recruited in this study. The basic information of age, sex, height, weight, diabetes history and hypertension history were collected, and blood samples were collected to test blood pressure (BP), glucose (GLU), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Using polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) to determine genotype.

Results

The genotype frequencies of rs2505901 and rs12346650 have no statistical difference between HS case group and control group as well as after adjusted for age, sex, diabetes history, hypertension history, TC, TG, HDL-C and LDL-C (P>0.05). Further stratification analysis by sex indicated that the dominant genetic model of rs2505901, the additive and recessive model of rs12346650 showed statistical significance for male HS and OR (95%CI) were 0.641 (0.417-0.984), 1.369 (1.020-1.836) and 2.092 (1.243-3.520) respectively. But the association weren’t significant after adjusted for confounding factors as above. For female, the receive model of rs12346650 showed significantly association with HS and the OR(95%CI) was 0.318 (0.114-0.891) after adjusted for confounding factors.

Conclusion

The finding in the present study suggested that there was weak association between MIR938 and TGFBR1 genetic polymorphisms and HS.

Key words: Single nucleotide polymorphisms, Hemorrhagic stroke, Transforming growth factor βreceptor 1, MicroRNA-938

Bo Song, Yun Cheng, Yuzhang Jiang, Chong Shen, Yong Xue, Yinghui Li. Association study between microRNA-938 and TGFBR1 single nucleotide polymorphisms and hemorrhagic stroke[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2019, 09(04): 205-209.

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References 15

[1]	任艳军,李秀央,陈坤,等.大气颗粒物污染与脑卒中死亡的病例交叉研究[J].中华流行病学杂志, 2008, 29(9): 878-881.
[2]	Xue M,Del Bigio MR. Immune pre-activation exacerbates hemorrhagic brain injury in immature mouse brain[J]. J Neuroimmunol, 2005, 165(1-2): 75-82.
[3]	Petrov V,Fagard R,Lijnen P. Stimulation of collagen production by TGF-beta1 during differentiation of cardiac fibroblasts to myofibroblasts[J]. Hypertension, 2002, 39(2): 258-263.
[4]	赵兴.原发性高血压血清血管紧张素II和转化生长因子β1与动脉僵硬度的相关性研究[D].银川:宁夏医科大学, 2009.
[5]	刘玉英,王立启,朱世明.转化生长因子β1与高血压靶器官损害的关系[J].山东大学学报(医学版), 2007, 45(5): 495-498.
[6]	刘遂心,孙明,周宏研.转化生长因子β在肾血管性高血压大鼠左心室的表达及与左室肥厚和心肌纤维化的关系探讨[J].高血压杂志, 2001, 9(2): 142-145.
[7]	Ebner R,Chen R,Shum L, et al. Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor[J]. Science, 1993, 260(5112): 1344-1348.
[8]	沈冲. TGF-β信号通路基因多态性与原发性高血压的关联研究[D].北京:北京协和医学院, 2008.
[9]	Laterza D,Ritelli M,Zini A, et al. Novel pathogenic TGFBR1 and SMAD3 variants identified after cerebrovascular events in adult patients with Loeys-dietz syndrome[J]. Eur J Med Genet, 62(10): 103727.
[10]	陈金凤,王海茹,杨松,等.转化生长因子-β1受体2基因启动子区单核苷酸多态性与原发性高血压遗传易感性的关联[J].中华预防医学杂志, 2012, 46(9): 825-830.
[11]	郭炜,董稚明,郭艳丽,等.转化生长因子βⅠ型受体Int7G24A和*6A多态性与贲门腺癌发病风险的相关性研究[J].肿瘤, 2016, 31(4): 332-338.
[12]	Shi Y,Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus[J]. Cell, 2003, 113(6): 685-700.
[13]	Moore-Smith L,Pasche B. TGFBR1 signaling and breast cancer[J]. J Mammary Gland Biol Neoplasia, 2011, 16(2): 89-95.
[14]	Mazzocca A,Fransvea E,Lavezzari G, et al. Inhibition of transforming growth factor beta receptor I kinase blocks hepatocellular carcinoma growth through neo-angiogenesis regulation[J]. Hepatology, 2009, 50(4): 1140-1151.
[15]	Yekta S,Shih IH,Bartel DP. MicroRNA-directed cleavage of HOXB8 mRNA[J]. Science, 2004, 304(5670): 594-596.

SNPs	引物设计(5 ’-3 ’)	等位基因（内切酶识别）	限制性内切酶	PCR产物及酶切片段长度（bp）
rs12346650	Forward: 5 ’AGGATGGACAAATGAGCAGAA 3 ’	G/A (G)	AvaII	110
rs12346650	Reward: 5 ’ACTTTGAATAACTGCACCAGGTC 3 ’	G/A (G)	AvaII	110
rs2505901	Forward: 5 ’ATGGGGCCCTGGATTATTAGGTT 3 ’	C/T (T)	BseLI	588
rs2505901	Reward: 5 ’TCGGCTTGACCATTTGCATCTT 3 ’	C/T (T)	BseLI	588

SNPs	引物设计(5 ’-3 ’)	等位基因（内切酶识别）	限制性内切酶	PCR产物及酶切片段长度（bp）
rs12346650	Forward: 5 ’AGGATGGACAAATGAGCAGAA 3 ’	G/A (G)	AvaII	110
rs12346650	Reward: 5 ’ACTTTGAATAACTGCACCAGGTC 3 ’	G/A (G)	AvaII	110
rs2505901	Forward: 5 ’ATGGGGCCCTGGATTATTAGGTT 3 ’	C/T (T)	BseLI	588
rs2505901	Reward: 5 ’TCGGCTTGACCATTTGCATCTT 3 ’	C/T (T)	BseLI	588

特征变量	病例组（n=239）	对照组（n=993）	χ²/t值	P值
男性	57.9%	40.3%	24.597	<0.001
年龄（岁）	61.75±13.58	63.61±9.09	1.912	<0.001
高血压	74.4%	44.2%	71.578	<0.001
收缩压（mmHg）	155.43±27.96	134.30±19.43	11.166	<0.001
舒张压（mmHg）	93.45±19.99	80.86±12.34	10.821	<0.001
TC（mmol/L）	4.32±1.10	5.32±0.96	12.792	0.013
HDL-C（mmol/L）	1.34±0.36	1.44±0.26	4.212	<0.001
LDL-C（mmol/L）	2.70±0.86	2.29±0.70	6.489	<0.001
TG（mmol/L）	1.52±1.28	1.57±0.88	0.732	<0.001
Ⅱ型糖尿病	7.5%	10.3%	1.702	0.191
GLU（mmol/L）	6.84±2.23	5.97±1.36	4.285	<0.001

特征变量	病例组（n=239）	对照组（n=993）	χ²/t值	P值
男性	57.9%	40.3%	24.597	<0.001
年龄（岁）	61.75±13.58	63.61±9.09	1.912	<0.001
高血压	74.4%	44.2%	71.578	<0.001
收缩压（mmHg）	155.43±27.96	134.30±19.43	11.166	<0.001
舒张压（mmHg）	93.45±19.99	80.86±12.34	10.821	<0.001
TC（mmol/L）	4.32±1.10	5.32±0.96	12.792	0.013
HDL-C（mmol/L）	1.34±0.36	1.44±0.26	4.212	<0.001
LDL-C（mmol/L）	2.70±0.86	2.29±0.70	6.489	<0.001
TG（mmol/L）	1.52±1.28	1.57±0.88	0.732	<0.001
Ⅱ型糖尿病	7.5%	10.3%	1.702	0.191
GLU（mmol/L）	6.84±2.23	5.97±1.36	4.285	<0.001

SNPs	组别	基因型，OR（95%CI）				等位基因
SNPs	组别	WT/HT/MT	相加模型	显性模型	隐性模型	常见/少见	OR（95%CI)
rs2505901	?	CC/CT/TT	?	?	?	C/T	?
?	病例组	159/69/9	0.896（0.646~1.243）	0.858（0.581~1.267）	0.985（0.399~2.429）	387/87	0.857（0.663~1.107）
?	对照组	621/328/42	P=0.512	P=0.441	P=0.973	1570/412	χ²=1.398，P=0.237
rs12346650	?	GG/GA/AA	?	?	?	G/A	?
?	病例组	84/116/37	0.983（0.742~1.303）	0.991（0.673~1.460）	0.953（0.545~1.666）	284/190	0.1.094（0.892~1.343）
?	对照组	371/488/132	P=0.907	P=0.965	P=0.638	1230/752	χ²=0.743，P=0.389

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