Association of Inflammatory Gene Polymorphisms With Ischemic Stroke in a Chinese Han Population

Nan Zhao; Xin Liu; Yongqin Wang; Xiaoqiu Liu; Jiana Li; Litian Yu; Liyuan Ma; Shuyu Wang; Hongye Zhang; Lisheng Liu; Jingbo Zhao; Xingyu Wang

Disclosures

J Neuroinflammation. 2012;9(162) 

In This Article

Results

The baseline and clinical characteristics of study participants are presented in Table 1. There were 1,124 ischemic stroke cases and 1,163 controls in this study. The control group was older than the case group. There were more individuals with hypertension in the control group and BMI was slightly higher compared to the case group.

Among the 51 polymorphisms, 11 SNPs had a MAF <5%. Two SNPs (interleukin 4 (IL4) rs2243250 (P = 0.001) and nitric oxide synthase 3 (endothelial cell) (NOS3) rs1800779 (P = 0.012)) deviated from Hardy-Weinberg equilibrium (HWE) in the control group and were excluded from subsequent analysis. Thus, 38 SNPs were selected for further analysis (see Additional file 1: Table S1).

As shown in Table 2, two SNPs in CCL11 were associated with ischemic stroke (P <0.05) in total study population. The ORs (95% CI; P value) were 1.47 (1.13 -1.92; 0.004) for CCL11 rs4795895 and 1.20 (1.01-1.43; 0.042) for CCL11 rs3744508. After adjustment for multiple testing, CCL11 rs4795895 remained significant (FDR = 0.152).

Hypertension is a major risk factor for stroke. Evidence has shown that stroke patients with or without hypertension exhibited different clinical features and different pathophysiology.[13] In consideration of the potential effect, hypertension stratification was decided on a priori. Odds ratios for the incidence of ischemic stroke are shown in Table 3. After stratification by hypertension and adjustment for age, sex, and BMI, 3 of 38 SNPs showed significant association (P <0.05) with ischemic stroke in the hypertensive group. These SNPs were in chemokine (C-C motif) receptor 2 (CCR2), chemokine (C-C motif) receptor 5 (CCR5) and CCL11. The ORs (95% CI; P value) were 1.26 (1.06 - 1.49; 0.009) for CCR2 rs1799864, 1.23 (1.06 - 1.42; 0.007) for CCR5 rs1799987 and 1.45 (1.05 - 1.99; 0.023) for CCL11 rs4795895. The FDR values were 0.152, 0.152 and 0.291, respectively.

In the non-hypertensive group, after adjustment for age, sex and BMI, there were six SNPs associated with stroke. The ORs (95% CI; P value) of these SNPs were 1.64 (1.20 - 2.24; 0.002) for CCL11 rs3744508, 1.56 (1.14 - 2.14; 0.006) for leukotriene C4 synthase (LTC4S) rs730012, 1.48 (1.02 - 2.00; 0.009) for FcepsilonRI-β (FCER1B) rs569108, 1.28 (1.03 - 1.59; 0.028) for lymphotoxin α (LTA) rs909253, 1.30 (1.07 - 1.59; 0.009) for transforming growth factor β1 (TGFB1) rs1800469 and 1.67 (1.05 - 2.66; 0.032) for CCL11 rs4795895. After correction for multiple testing, five SNPs, CCL11 rs3744508, LTC4S rs730012, FCER1B rs569108, TGFB1 rs1800469, LTA rs909253, had FDR values less than 0.20 (Table 3). We tested the interaction between hypertension and genetic variants. There was no interaction detected between any genetic variants and hypertension status (data not shown).

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