白細胞介素-6基因174G/C多態性與缺血性腦卒中風險相關性的Meta分析_《中國循證醫學雜志》

作者：

黎炳護 , 張莉莉 , 尹延偉 , 皮燕 , 楊清武 , 方傳勤 , 高長越 , 王景周 ,  李敬誠

第三軍醫大學大坪醫院野戰外科研究所神經內科（重慶 400042）;

關鍵詞：

缺血性腦卒中白細胞介素-6 174G/C 基因多態性 Meta分析

DOI：

10.7507/1672-2531.20120091

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目的　探討白細胞介素-6（interleukin-6，IL-6）基因174G/C多態性與缺血性腦卒中（ischemic stroke，IS）風險的相關性。
方法　計算機檢索CBM、CNKI、PubMed、MEDLINE 和 EMbase數據庫，收集從建庫至2011年8月間關于IL-6基因174G/C多態性與IS風險相關性的病例對照研究，由兩名研究者獨立進行資料提取、質量評價并交叉核對后，采用RevMan 5.1.2和Stata 11.0軟件對符合標準的文獻進行Meta分析。
結果　共納入12個研究，2 537例患者和2 767例對照。各遺傳模型Meta分析結果顯示：IL-6基因174G/C多態性與IS風險的相關性無統計學意義［共顯性遺傳模型：G/C vs. G/G：OR=0.98，95%CI（0.78，1.24）；C/C vs. G/G：OR=0.75，95%CI（0.38，1.50）；顯性遺傳模型：OR=0.93，95%CI（0.68，1.28）；隱性遺傳模型：OR=0.80，95%CI（0.45，1.42）］。基于人種的亞組分析結果顯示兩者相關性無統計學意義，而基于對照來源的亞組分析結果顯示，對照人群為醫院來源的亞組中IL-6基因174G/C多態性是IS的保護因素［共顯性遺傳模型：G/C vs. G/G：OR=0.56，95%CI（0.40，0.79）；C/C vs. G/G：OR=0.17，95%CI（0.11，0.27）；顯性遺傳模型：OR=0.40，95%CI（0.29，0.55）；隱性遺傳模型：OR=0.24，95%CI（0.16，0.37）］。
結論　基于目前研究結果顯示，IL-6基因174G/C多態性與IS風險無明顯相關性。受納入研究質量和數量限制，上述結論尚待開展更多高質量的前瞻性研究進一步驗證。

引用本文： 黎炳護,張莉莉,尹延偉,皮燕,楊清武,方傳勤,高長越,王景周,李敬誠. 白細胞介素-6基因174G/C多態性與缺血性腦卒中風險相關性的Meta分析. 中國循證醫學雜志, 2012, 12(5): 563-569. doi: 10.7507/1672-2531.20120091 復制

1.	Lloyd-Jones D, Adams RJ, Brown TM, et al. Executive summary: heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation, 2010, 121(7): 948-954.
2.	Dichgans M. Genetics of ischaemic stroke. Lancet Neurol, 2007, 6(2): 149-161.
3.	Humphries SE, Morgan L. Genetic risk factors for stroke and carotid atherosclerosis: insights into pathophysiology from candidate gene approaches. Lancet Neurol, 2004, 3(4): 227-235.
4.	Castillo J, Rodriguez I. Biochemical changes and inflammatory response as markers for brain ischaemia: molecular markers of diagnostic utility and prognosis in human clinical practice. Cerebrovasc Dis, 2004, 17 (Suppl 1): 7-18.
5.	Pasarica D, Gheorghiu M, Topârceanu F, et al. Neurotrophin-3, TNF-α and IL-6 relations in serum and cerebrospinal fluid of ischemic stroke patients. Roum Arch Microbiol Immunol, 2005, 64(1-4): 27-33.
6.	Smith CJ, Emsley HC, Gavin CM, et al. Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol, 2004, 4: 2.
7.	Georges JL, Loukaci V, Poirier O, et al. Interleukin-6 gene polymorphisms and susceptibility to myocardial infarction: the ECTIM study. Etude Cas-TÊmoin de l’infarctus du Myocarde. J Mol Med, 2001, 79(5-6): 300-305.
8.	Strand M, Soderstrom I, Wiklund PG. Polymorphisms at the Osteoprotegerin and Interleukin-6 Genes in Relation to First-Ever Stroke. Cerebrovasc Dis, 2007, 24(5): 418-425.
9.	Marousi S, Antonacopoulou A, Karakantza M. Functional in?ammatory genotypes: are they useful in the prediction of age of onset and long-term outcome of an ischaemic stroke? J Neurol, 2011, 258 (Suppl 1): S10.
10.	Ma S, Jiang LY, Dong ML, et al. Relation of polymorphism at -174 site of the interleukin-6 gene control region with the occurrence and development of disease in aged patients with cerebral infarction. Chinese Journal of Clinical Rehabilitation, 2004, 8(22): 4508-4509.
11.	Chakraborty B, Agarwal S, Vishnoi G. Interleukin-6 Promoter Polymorphism Predicts Stroke Severity and Outcome in Acute Ischemic Stroke Patients from North India. Stroke, 2011, 42(3): e266.
12.	Revilla M, Obach V, Cervera A, et al. A -174G/C polymorphism of the interleukin-6 gene in patients with lacunar infarction. Neurosci Lett, 2002, 324(1): 29-32.
13.	Pola R, Flex A, Gaetani E, et al. Synergistic effect of 174 G/C polymorphism of the interleukin-6 gene promoter and 469 E/K polymorphism of the intercellular adhesion molecule-1 gene in Italian patients with history of ischemic stroke. Stroke, 2003, 34(4): 881-885.
14.	Greisenegger S, Endler G, Haering D, et al. The (174) G/C polymorphism in the interleukin-6 gene is associated with the severity of acute cerebrovascular events. Thromb Res, 2003, 110(4): 181-186.
15.	Flex A, Gaetani E, Papaleo P, et al. Proin?ammatory genetic pro?les in subjects with history of ischemic stroke. Stroke, 2004, 35(10): 2270-2275.
16.	Balding J, LivingstoneWJ, Pittock SJ, et al. The IL-6 G-174C polymorphism may be associated with ischaemic stroke in patients without a history of hypertension. Ir J Med Sci, 2004, 173(4): 200-203.
17.	Chamorro A, Revilla M, Obach V, et al. The -174G/C polymorphism of the interleukin 6 gene is a hallmark of lacunar stroke and not other ischemic stroke phenotypes. Cerebrovasc Dis, 2005, 19(2): 91-95.
18.	Karahan ZC, Deda G, Sipahi T, et al. TNF-alpha -308G/A and IL-6 -174 G/C polymorphisms in the Turkish pediatric stroke patients. Thromb Res, 2005, 115(5): 393-398.
19.	Lalouschek W, Schillinger M, Hsieh K, et al. Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events. Clin Chem Lab Med, 2006, 44(8): 918-923.
20.	Banerjee I, Gupta V, Ahmed T, et al. Inflammatory system gene polymorphism and the risk of stroke: A case-control study in an Indian population. Brain Res Bull, 2008, 75(1): 158-165.
21.	Tong Y, Wang Z, Geng Y, et al. The association of functional polymorphisms of IL-6 gene promoter with ischemic stroke: analysis in two Chinese populations. Biochem Biophys Res Commun, 2010, 391(1): 481-485.
22.	劉東芳, 陳乃耀, 王大力, 等. 唐山地區漢族人群腦梗死患者IL-6基因-174G/C多態性研究. 現代預防醫學, 2010, 37(18): 3419-3422.
23.	尤勁松, 黃培新, 劉茂才, 等. 腦梗死患者ICAM-1基因K469E及IL-6基因-174G/C多態性研究. 中國老年學雜志, 2007, 27(16): 1580-1582.
24.	張艷萍, 張蘊莉, 方伯言. 炎性因子IL-6、ICAM-1基因多態性與腦梗死的相關性. 醫學綜述, 2008；14(4): 539-541.
25.	張江, 王大力, 陳乃耀, 等. 唐山地區漢族人群腦梗死患者IL-6基因-174G/C多態性研究. 中風與神經疾病雜志, 2010, 27(9): 837-839.
26.	肖慧, 谷文萍, 梁靜, 等. 白細胞介素-6基因多態性與動脈粥樣硬化性腦梗死的關系. 中國神經精神疾病雜志, 2011, 37(1): 11-14.
27.	全國第四屆腦血管病學術會議. 各類腦血管病的診斷要點. 中華神經科雜志, 1996, 29(6): 379-380.
28.	Wood PH. Appreciating the consequences of disease: the international classification of impairments, disabilities, and handicaps. WHO Chron, 1980, 34(10): 376-380.
29.	Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute. www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed Oct 20, 2011).
30.	Clark WM, Rinker LG, Lessov NS, et al. Time course of IL-6 expression in experimental CNS ischemia. Neurol Res, 1999, 21(3): 287-292.

1. Lloyd-Jones D, Adams RJ, Brown TM, et al. Executive summary: heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation, 2010, 121(7): 948-954.
2. Dichgans M. Genetics of ischaemic stroke. Lancet Neurol, 2007, 6(2): 149-161.
3. Humphries SE, Morgan L. Genetic risk factors for stroke and carotid atherosclerosis: insights into pathophysiology from candidate gene approaches. Lancet Neurol, 2004, 3(4): 227-235.
4. Castillo J, Rodriguez I. Biochemical changes and inflammatory response as markers for brain ischaemia: molecular markers of diagnostic utility and prognosis in human clinical practice. Cerebrovasc Dis, 2004, 17 (Suppl 1): 7-18.
5. Pasarica D, Gheorghiu M, Topârceanu F, et al. Neurotrophin-3, TNF-α and IL-6 relations in serum and cerebrospinal fluid of ischemic stroke patients. Roum Arch Microbiol Immunol, 2005, 64(1-4): 27-33.
6. Smith CJ, Emsley HC, Gavin CM, et al. Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol, 2004, 4: 2.
7. Georges JL, Loukaci V, Poirier O, et al. Interleukin-6 gene polymorphisms and susceptibility to myocardial infarction: the ECTIM study. Etude Cas-TÊmoin de l’infarctus du Myocarde. J Mol Med, 2001, 79(5-6): 300-305.
8. Strand M, Soderstrom I, Wiklund PG. Polymorphisms at the Osteoprotegerin and Interleukin-6 Genes in Relation to First-Ever Stroke. Cerebrovasc Dis, 2007, 24(5): 418-425.
9. Marousi S, Antonacopoulou A, Karakantza M. Functional in?ammatory genotypes: are they useful in the prediction of age of onset and long-term outcome of an ischaemic stroke? J Neurol, 2011, 258 (Suppl 1): S10.
10. Ma S, Jiang LY, Dong ML, et al. Relation of polymorphism at -174 site of the interleukin-6 gene control region with the occurrence and development of disease in aged patients with cerebral infarction. Chinese Journal of Clinical Rehabilitation, 2004, 8(22): 4508-4509.
11. Chakraborty B, Agarwal S, Vishnoi G. Interleukin-6 Promoter Polymorphism Predicts Stroke Severity and Outcome in Acute Ischemic Stroke Patients from North India. Stroke, 2011, 42(3): e266.
12. Revilla M, Obach V, Cervera A, et al. A -174G/C polymorphism of the interleukin-6 gene in patients with lacunar infarction. Neurosci Lett, 2002, 324(1): 29-32.
13. Pola R, Flex A, Gaetani E, et al. Synergistic effect of 174 G/C polymorphism of the interleukin-6 gene promoter and 469 E/K polymorphism of the intercellular adhesion molecule-1 gene in Italian patients with history of ischemic stroke. Stroke, 2003, 34(4): 881-885.
14. Greisenegger S, Endler G, Haering D, et al. The (174) G/C polymorphism in the interleukin-6 gene is associated with the severity of acute cerebrovascular events. Thromb Res, 2003, 110(4): 181-186.
15. Flex A, Gaetani E, Papaleo P, et al. Proin?ammatory genetic pro?les in subjects with history of ischemic stroke. Stroke, 2004, 35(10): 2270-2275.
16. Balding J, LivingstoneWJ, Pittock SJ, et al. The IL-6 G-174C polymorphism may be associated with ischaemic stroke in patients without a history of hypertension. Ir J Med Sci, 2004, 173(4): 200-203.
17. Chamorro A, Revilla M, Obach V, et al. The -174G/C polymorphism of the interleukin 6 gene is a hallmark of lacunar stroke and not other ischemic stroke phenotypes. Cerebrovasc Dis, 2005, 19(2): 91-95.
18. Karahan ZC, Deda G, Sipahi T, et al. TNF-alpha -308G/A and IL-6 -174 G/C polymorphisms in the Turkish pediatric stroke patients. Thromb Res, 2005, 115(5): 393-398.
19. Lalouschek W, Schillinger M, Hsieh K, et al. Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events. Clin Chem Lab Med, 2006, 44(8): 918-923.
20. Banerjee I, Gupta V, Ahmed T, et al. Inflammatory system gene polymorphism and the risk of stroke: A case-control study in an Indian population. Brain Res Bull, 2008, 75(1): 158-165.
21. Tong Y, Wang Z, Geng Y, et al. The association of functional polymorphisms of IL-6 gene promoter with ischemic stroke: analysis in two Chinese populations. Biochem Biophys Res Commun, 2010, 391(1): 481-485.
22. 劉東芳, 陳乃耀, 王大力, 等. 唐山地區漢族人群腦梗死患者IL-6基因-174G/C多態性研究. 現代預防醫學, 2010, 37(18): 3419-3422.
23. 尤勁松, 黃培新, 劉茂才, 等. 腦梗死患者ICAM-1基因K469E及IL-6基因-174G/C多態性研究. 中國老年學雜志, 2007, 27(16): 1580-1582.
24. 張艷萍, 張蘊莉, 方伯言. 炎性因子IL-6、ICAM-1基因多態性與腦梗死的相關性. 醫學綜述, 2008；14(4): 539-541.
25. 張江, 王大力, 陳乃耀, 等. 唐山地區漢族人群腦梗死患者IL-6基因-174G/C多態性研究. 中風與神經疾病雜志, 2010, 27(9): 837-839.
26. 肖慧, 谷文萍, 梁靜, 等. 白細胞介素-6基因多態性與動脈粥樣硬化性腦梗死的關系. 中國神經精神疾病雜志, 2011, 37(1): 11-14.
27. 全國第四屆腦血管病學術會議. 各類腦血管病的診斷要點. 中華神經科雜志, 1996, 29(6): 379-380.
28. Wood PH. Appreciating the consequences of disease: the international classification of impairments, disabilities, and handicaps. WHO Chron, 1980, 34(10): 376-380.
29. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute. www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed Oct 20, 2011).
30. Clark WM, Rinker LG, Lessov NS, et al. Time course of IL-6 expression in experimental CNS ischemia. Neurol Res, 1999, 21(3): 287-292.

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白細胞介素-6基因174G/C多態性與缺血性腦卒中風險相關性的Meta分析

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《中國循證醫學雜志》

白細胞介素-6基因174G/C多態性與缺血性腦卒中風險相關性的Meta分析

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