Association between MTHFR C677T Polymorphism and Young Adult Ischemic Stroke in Chinese Population: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 CHENJia ¹ , HERu-lin ² , LANGYing ¹ ,  XUZhi-qiang ¹

1. Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, China;
2. Department of Anesthesiology, PLA 123 Hospital, Bengbu 233000, China;

Corresponding author：

XUZhi-qiang, Email: xzq881@163.com

Keywords：

MTHFR; SNP; Ischemic stroke; Systematic review; Meta-analysis; Case-control study; Young and middle-aged

DOI：

10.7507/1672-2531.20140076

Video：

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Objective To systematically evaluate the association between MTHFR gene C677T polymorphism and susceptibility to young and middle-aged adult ischemic stroke among Chinese population. Methods Such databases as PubMed, EMbase, The Cochrane Library (Issue 11, 2013), CBM, CNKI, VIP and WanFang Data were systemically searched to collect case-control studies published from Jan 1990 to Dec 2013. RevMan 5.2 was used to quantitatively analyzed the qualified and included studies, the pooled odds ratio (ORs) with 95% confidence interval (CI) were calculated; Stata 12.0 software were used for sensitivity and publication bias analysis. Results A total of 10 studies were included, which involved 787 cases and 766 controls. The results of meta-analysis showed that, in overall young and middle-aged adult group (aged less than 60), individuals that carried T allele risked more with ischemic stroke than those carried C allele (OR=1.42, 95%CI 1.07 to 1.89, P=0.02); more susceptibility to ischemic stroke was found among people of TT genotype compared with those of CC genotype (OR=2.11, 95%CI 1.58 to 2.81, P=0.00), as well as those of TT+TC genotype compared with CC genotype (OR=1.97, 95%CI 1.55 to 2.51, P=0.00), and those of TT genotype compared with TC+CC genotype (OR=1.42, 95%CI 1.13 to 1.77, P=0.00). Increased risk was also observed in TT+TC genotype compared with CC genotype in young adult subgroup (aged less than 45) (OR=1.66, 95%CI 1.19 to 2.32, P=0.00). Conclusion MTHFR gene C677T polymorphism is significantly associated with susceptibility to young and middle-aged adult ischemic stroke among Chinese population, and more risk may exist in middle-aged adult population.

Citation： CHENJia, HERu-lin, LANGYing, XUZhi-qiang. Association between MTHFR C677T Polymorphism and Young Adult Ischemic Stroke in Chinese Population: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(4): 435-442. doi: 10.7507/1672-2531.20140076 Copy

1.	侯东哲, 高晓刚, 孙岩伟, 等.青年脑卒中分布状况及危险因素分析.中国实验诊断学, 2010, 14(7):1156-1158.
2.	Pezzini A, Del Zotto E, Padovani A.Homocysteine and cerebral ischemia:pathogenic and therapeutical implications.Curr Med Chem, 2007, 14(3):249-263.
3.	Friso S, Chois W, Girelli D, et al.A common mutation in the 5, 10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status.P Natl Acad Sci USA, 2002, 99(8):5606-5611.
4.	刘鸣, 张苏明, 饶明俐.中国急性缺血性脑卒中诊治指南2010.中华神经科杂志, 2010, 43(2):146-153.
5.	Stang A.Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.Eur J Epidemiol, 2010, 25(9):603-605.
6.	高海凤, 刘建国, 张哲成, 等.高同型半胱氨酸血症及MTHFR基因与中青年脑梗死的研究.天津医药, 2003, 31(10):627-629.
7.	林琳, 周维智, 刘晓红, 等.血浆同型半胱氨酸水平及mthfr基因多态性与中青年脑卒中的相关研究.神经病学与神经康复学杂志, 2004, 1(4):216-219.
8.	王利军, 牛小媛, 琚小红, 等.MTHFR基因多态性及血浆同型半胱氨酸水平与中青年人脑梗死的关系.中风与神经疾病杂志, 2006, 23(4):478-481.
9.	方乐, 王田蔚, 邵延坤, 等.青年缺血性脑卒中与MTHFR C677T、CBS844ins68基因多态性的关系.吉林大学学报·医学版, 2007, 33(2):310-313.
10.	李海宁, 杨申, 侯晓霖, 等.血浆Hcy水平及MTHFR基因C677T多态性与宁夏中青年缺血性脑卒中的关系研究.宁夏医学杂志, 2007, 29(8):685-687.
11.	南光贤, 王利平.MTHFR C677T和CBS T833C G919A基因突变与青年缺血性脑卒中的关系.中国实验诊断学, 2007, 11(11):1538-1540.
12.	高娟, 孙亚菲, 李永乐, 等.青年脑梗死患者同型半胱氨酸、5, 10-亚甲基四氢叶酸还原酶基因多态性检测.郑州大学学报·医学版, 2008, 43(3):570-573.
13.	Shi CN, Kang XX, Wang YJ, et al.The coagulation factor V Leiden, MTHFRC677T variant and eNOS 4ab polymorphism in young Chinese population with ischemic stroke.Clin Chim Acta, 2008, 396(1):7-9.
14.	Zhang Y, Xie RP, Shen Y, et al.Interaction between methylenetetrahydrofolate reductase C677T gene polymorphism and sleep duration on risk of stroke pathogenesis.Beijing Da Xue Xue Bao, 2008, 40(3):262-269.
15.	张成森, 刘翠薇, 潘旭东, 等.N5, N10-亚甲基四氢叶酸还原酶基因多态性与青年脑梗死的关系.中国医药, 2012, 7(5):570-572.
16.	Selhub J.Homocysteine metabolism.Ann Rev Nutr, 1999, 19(1):217-246.
17.	张琛, 朱惠莲.B族维生素干预血浆同型半胱氨酸水平防治心脑血管疾病作用的Meta分析.中国循证医学杂志, 2009, 9(1):55-62.
18.	Boysen G, Brander T, Christensen H, et al.Homocysteine and risk of recurrent stroke.Stroke, 2003, 34(5):1258-1261.
19.	Zheng YZ, Tong J, Do XP, et al.Prevalence of methylenetetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population.Brit J Haematol, 2000, 109(4):870-874.
20.	Li Z, Sun L, Zhang H, et al.Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke:a multicenter case-control study in China.Stroke, 2003, 34(9):2085-2090.
21.	傅毅, 刘建荣, 倪培华, 等.同型半胱氨酸及代谢酶基因多态性与脑卒中的相关性研究.中华老年医学杂志, 2005, 24(06):413-417.
22.	Shen CD, Zhang WL, Sun K, et al.Interaction of genetic risk factors confers higher risk for thrombotic stroke in male Chinese:a multicenter case-control study.Ann Hum Genet, 2007, 71(5):620-629.

1. 侯东哲, 高晓刚, 孙岩伟, 等.青年脑卒中分布状况及危险因素分析.中国实验诊断学, 2010, 14(7):1156-1158.
2. Pezzini A, Del Zotto E, Padovani A.Homocysteine and cerebral ischemia:pathogenic and therapeutical implications.Curr Med Chem, 2007, 14(3):249-263.
3. Friso S, Chois W, Girelli D, et al.A common mutation in the 5, 10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status.P Natl Acad Sci USA, 2002, 99(8):5606-5611.
4. 刘鸣, 张苏明, 饶明俐.中国急性缺血性脑卒中诊治指南2010.中华神经科杂志, 2010, 43(2):146-153.
5. Stang A.Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.Eur J Epidemiol, 2010, 25(9):603-605.
6. 高海凤, 刘建国, 张哲成, 等.高同型半胱氨酸血症及MTHFR基因与中青年脑梗死的研究.天津医药, 2003, 31(10):627-629.
7. 林琳, 周维智, 刘晓红, 等.血浆同型半胱氨酸水平及mthfr基因多态性与中青年脑卒中的相关研究.神经病学与神经康复学杂志, 2004, 1(4):216-219.
8. 王利军, 牛小媛, 琚小红, 等.MTHFR基因多态性及血浆同型半胱氨酸水平与中青年人脑梗死的关系.中风与神经疾病杂志, 2006, 23(4):478-481.
9. 方乐, 王田蔚, 邵延坤, 等.青年缺血性脑卒中与MTHFR C677T、CBS844ins68基因多态性的关系.吉林大学学报·医学版, 2007, 33(2):310-313.
10. 李海宁, 杨申, 侯晓霖, 等.血浆Hcy水平及MTHFR基因C677T多态性与宁夏中青年缺血性脑卒中的关系研究.宁夏医学杂志, 2007, 29(8):685-687.
11. 南光贤, 王利平.MTHFR C677T和CBS T833C G919A基因突变与青年缺血性脑卒中的关系.中国实验诊断学, 2007, 11(11):1538-1540.
12. 高娟, 孙亚菲, 李永乐, 等.青年脑梗死患者同型半胱氨酸、5, 10-亚甲基四氢叶酸还原酶基因多态性检测.郑州大学学报·医学版, 2008, 43(3):570-573.
13. Shi CN, Kang XX, Wang YJ, et al.The coagulation factor V Leiden, MTHFRC677T variant and eNOS 4ab polymorphism in young Chinese population with ischemic stroke.Clin Chim Acta, 2008, 396(1):7-9.
14. Zhang Y, Xie RP, Shen Y, et al.Interaction between methylenetetrahydrofolate reductase C677T gene polymorphism and sleep duration on risk of stroke pathogenesis.Beijing Da Xue Xue Bao, 2008, 40(3):262-269.
15. 张成森, 刘翠薇, 潘旭东, 等.N5, N10-亚甲基四氢叶酸还原酶基因多态性与青年脑梗死的关系.中国医药, 2012, 7(5):570-572.
16. Selhub J.Homocysteine metabolism.Ann Rev Nutr, 1999, 19(1):217-246.
17. 张琛, 朱惠莲.B族维生素干预血浆同型半胱氨酸水平防治心脑血管疾病作用的Meta分析.中国循证医学杂志, 2009, 9(1):55-62.
18. Boysen G, Brander T, Christensen H, et al.Homocysteine and risk of recurrent stroke.Stroke, 2003, 34(5):1258-1261.
19. Zheng YZ, Tong J, Do XP, et al.Prevalence of methylenetetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population.Brit J Haematol, 2000, 109(4):870-874.
20. Li Z, Sun L, Zhang H, et al.Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke:a multicenter case-control study in China.Stroke, 2003, 34(9):2085-2090.
21. 傅毅, 刘建荣, 倪培华, 等.同型半胱氨酸及代谢酶基因多态性与脑卒中的相关性研究.中华老年医学杂志, 2005, 24(06):413-417.
22. Shen CD, Zhang WL, Sun K, et al.Interaction of genetic risk factors confers higher risk for thrombotic stroke in male Chinese:a multicenter case-control study.Ann Hum Genet, 2007, 71(5):620-629.

Chinese Journal of Evidence-Based Medicine

Association between MTHFR C677T Polymorphism and Young Adult Ischemic Stroke in Chinese Population: A Meta-Analysis

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