Objective To analyze the association between ？1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis. Methods We carried out a systematic electronic search in PubMed, BIOSIS Previews, Science Direct, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Weipu database and WANGFANG Database. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the association. Results 7 studies were included. There was no significant association between IL-10 ？1082A/G polymorphism and IS risk under all genetic models in overall estimates (A vs. G: OR = 1.23,95%CI = 0.85–1.79;AA vs. GG: OR = 1.01,95%CI = 0.47–2.19; AG vs. GG: OR = 0.76, 95%CI = 0.38–1.55; AA+AG vs. GG: OR = 0.89,95%CI = 0.46–1.73; AA vs. AG+GG: OR = 1.39, 95%CI = 0.91–2.13). Similarly, no associations were found in subgroup analysis based on ethnicity and source of controls. However, removing the study deviating from Hardy–Weinberg equilibrium (HWE) produced statistically significant associations for overall estimates under recessive model(AA VS. AG+GG OR 1.58, 95% CI 1.04–2.42) and among Asians in all genetic models (A VS.G OR 1.64, 95% CI 1.07–2.53; AA vs. GG OR1.91, 95% CI 1.31–2.80; AG vs. GG OR1.44, 95% CI 1.09–1.91; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01;AA VS. AG+GG OR 1.79, 95% CI 1.07–3.00). Even after Bonferroni correction, the associations were observed still significantly in Asians under the two models (AA vs. GG OR1.91, 95% CI 1.31–2.80, P = 0.0008; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01, P = 0.001). Conclusion This meta-analysis indicates that IL10 ？1082 A/G polymorphism is associated with IS susceptibility in Asians and the ？1082 A allele may increase risk of IS in Asians. Considering the sample size is small and between-study heterogeneity is remarkable, more studies with subtle design are warranted in future.
Munshi A, Rajeshwar K, Kaul S, Al-Hazzani A, Alshatwi AA, et al. (2010) Interleukin-10-1082 promoter polymorphism and ischemic stroke risk in a South Indian population. Cytokine 52: 221–224. doi: 10.1016/j.cyto.2010.09.013
Marousi S, Antonacopoulou A, Kalofonos H, Papathanasopoulos P, Karakantza M, et al. (2011) Functional inflammatory genotypes in ischemic stroke: could we use them to predict age of onset and long-term outcome? Stroke Res Treat 2011: 792923. doi: 10.4061/2011/792923
Liesz A, Suri-Payer E, Veltkamp C, Doerr H, Sommer C, et al. (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15: 192–199. doi: 10.1038/nm.1927
Eskdale J, Gallagher G, Verweij CL, Keijsers V, Westendorp RG, et al. (1998) Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci U S A 95: 9465–9470. doi: 10.1073/pnas.95.16.9465
Kilpinen S, Huhtala H, Hurme M (2002) The combination of the interleukin-1alpha (IL-1alpha-889) genotype and the interleukin-10 (IL-10 ATA) haplotype is associated with increased interleukin-10 (IL-10) plasma levels in healthy individuals. Eur Cytokine Netw 13: 66–71.
Marousi S, Ellul J, Antonacopoulou A, Gogos C, Papathanasopoulos P, et al. (2011) Functional polymorphisms of interleukin 4 and interleukin 10 may predict evolution and functional outcome of an ischaemic stroke. Eur J Neurol 18: 637–643. doi: 10.1111/j.1468-1331.2010.03228.x
Tuttolomondo A, Di Raimondo D, Forte GI, Casuccio A, Vaccarino L, et al. (2012) Single nucleotide polymorphisms (SNPs) of pro-inflammatory/anti-inflammatory and thrombotic/fibrinolytic genes in patients with acute ischemic stroke in relation to TOAST subtype. Cytokine 58: 398–405. doi: 10.1016/j.cyto.2012.02.012
Sultana S, Kolla VK, Jeedigunta Y, Penagaluru PK, Joshi S, et al. (2011) Tumour necrosis factor alpha and interleukin 10 gene polymorphisms and the risk of ischemic stroke in south Indian population. J Genet 90: 361–364. doi: 10.1007/s12041-011-0079-5
Jin L, Ni PH, Wu JM, Fu Yi, Ge HL (2011) The correlation between gene polymorphism of IL-10-819C/T and -1082G/A and cerebral infarction (In Chinese). Laboratory Medicine 26: 717–721.
Zhang GZ, Pan SY, Du R, lu BX, Li W (2007) The relationship between interleukin-10 gene polymorphisms and cerebral infarction (In Chinese). Chin J Cerebrovasc Dis 4: 294–297.
Lin KX (2009) Study on The Relationship between Interleukin–10 Gene Polymorphisms and Cerebral Infarction. Unpublished MsD dissertation [MsD]: Fujian Medical University.
Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25: 603–605. doi: 10.1007/s10654-010-9491-z
Attia J, Thakkinstian A, D'Este C (2003) Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol 56: 297–303. doi: 10.1016/s0895-4356(03)00011-8
Egger M, Davey SG, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315: 629–634. doi: 10.1136/bmj.315.7109.629
Timasheva YR, Nasibullin TR, Zakirova AN, Mustafina OE (2008) Association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension in Tatars from Russia. Biochem Genet 46: 64–74. doi: 10.1007/s10528-007-9130-x
Xie GQ, Zhao LC, Li Y, Wang H, Liang LR, et al. (2008) The Relationship Between Interleukin-10 Gene -592A/C Polymorphism and Carotid Atherosclerosis (In Chinese). Molecular Cardiology of China 8: 305–309. doi: 10.1016/j.ijcard.2008.11.173
Park HK, Kim DH, Yun DH, Ban JY (2013) Association between IL10, IL10RA, and IL10RB SNPs and ischemic stroke with hypertension in Korean population. Mol Biol Rep 40: 1785–1790. doi: 10.1007/s11033-012-2232-5
Balding J, Livingstone WJ, Pittock SJ, Mynett-Johnson L, Ahern T, et al. (2004) The IL-6 G-174C polymorphism may be associated with ischaemic stroke in patients without a history of hypertension. Ir J Med Sci 173: 200–203. doi: 10.1007/bf02914551
Li H (2008) Study on Relationship among Polymorphisms of three Inflammatory Cytokines,Serum Level of Lipoprotein and Cerebral Infarction. Unpublished MsD dissertation [MsD]: Southern Medical University.
Xie G, Myint PK, Zaman MJ, Li Y, Zhao L, et al. (2013) Relationship of serum interleukin-10 and its genetic variations with ischemic stroke in a chinese general population. PLoS One 8: e74126. doi: 10.1371/journal.pone.0074126
Zhang GZ (2006) Correlation between Interleukin-1, 10,TNF-a,TNF-βGene Polymorphisms and Cerebral Infarction. Unpublished MsD dissertation [MsD]: First Military Medical University Southern Medical University.
Yadav S, Hasan N, Marjot T, Khan MS, Prasad K, et al. (2013) Detailed analysis of gene polymorphisms associated with ischemic stroke in South Asians. PLoS One 8: e57305. doi: 10.1371/journal.pone.0057305
Stoica AL, Stoica E, Constantinescu I, Uscatescu V, Ginghina C (2010) Interleukin-6 and interleukin-10 gene polymorphism, endothelial dysfunction, and postoperative prognosis in patients with peripheral arterial disease. J Vasc Surg 52: 103–109. doi: 10.1016/j.jvs.2010.01.088
Trompet S, Pons D, DE Craen AJ, Slagboom P, Shepherd J, et al. (2007) Genetic variation in the interleukin-10 gene promoter and risk of coronary and cerebrovascular events: the PROSPER study. Ann N Y Acad Sci 1100: 189–198. doi: 10.1196/annals.1395.018
Fei GZ, Svenungsson E, Frostegard J, Padyukov L (2004) The A-1087IL-10 allele is associated with cardiovascular disease in SLE. Atherosclerosis 177: 409–414. doi: 10.1016/j.atherosclerosis.2004.07.026
Bis JC, Heckbert SR, Smith NL, Reiner AP, Rice K, et al. (2008) Variation in inflammation-related genes and risk of incident nonfatal myocardial infarction or ischemic stroke. Atherosclerosis 198: 166–173. doi: 10.1016/j.atherosclerosis.2007.09.031
Thakkinstian A, McElduff P, D'Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24: 1291–1306. doi: 10.1002/sim.2010
Attia J, Thakkinstian A, D'Este C (2003) Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol 56: 297–303. doi: 10.1016/s0895-4356(03)00011-8
