Relationship between stroke and both NINJ2 gene polymorphism and its related serum cytokines

Abstract

Objective To investigate the relationship between NINJ2 gene polymorphism and stroke, and the differences of serum levels of tumor necrosis factor-αt (TNF-α), NGF, interleukin-6 (IL-6)and P-Selectin in healthy controls and patients under recovery stage. Methods Fifty-two patients with large-artery atherosclerosis (LAA) infarction, 85 patients with small-artery occlusion lacunar (SAO)infarction, 50 patients with intracerebral hemorrhage (ICH) and 66 healthy controls were included in this study. Genotypes of the 2 single nucleotide polymorphism (SNP) sites (rs12425791 and rs11833579) in NINJ2 gene were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) method. The differences of genotypes and alleles frequencies of the 2 SNP sites between each 2 different groups were analyzed and compared. Multinomial logistic regression was used to calculate the odds ratio (OR) of genotypes in each patient group, and 95% confidential interval (95% CI)was given. The serum levels ofTNF-α, NGF, IL-6 and P-Selectin were tested by ELISA method, and compared between groups and within group classified by genotypes. Results In regard to rs12425791 site, the frequencies of AG and AA+AG genotypes in LAA and SAO groups were significantly higher than those in control group (P＜0.05), while this difference was not found between the ICH group and control group (P＞0.05); the frequency of A allele in the SAO group was significantly higher than that in the control group (P＜0.05), while this difference was not found between the control group and both the LAA and ICH groups (P＞0.05). In regard to rs11833579 site, no significant differences in the genotypes and alleles were noted between all the patient groups and control group (P＞0.05). After adjusting the influence of other risk factors, the multinomial logistic regression analysis showed that the onset of stroke was still significantly associated with the AG genotype at rs12425791 site in the LAA group (OR=4.298,95%CI=1.430-12.922) and AG, AG+AA genotypes at rs12425791 site in the SAO group (OR=3.923 and 2.937, 95%CI= 1.417- 10.860 and 1.119-7.710). Neither genotypes in rs 11833579 site were significantly associated with the onset of stroke. No significant differences of serum levels of TNF-α, NGF, IL-6 and P-Selectin were noted between each patient group under recovery stage and control group (P＞0.05); in regard to rs12425791 site, the serum level of TNF in LAA group with different genotypes was significantly different (P＜0.05) and the serum level of P-Selectin in ICH group with different genotypes was significantly different (P＜0.05); in regard to rs11833579 site, the serum level of NGF in LAA group with different genotypes was statistically different (P＜0.05). Conclusion This SNP site (rs12425791)is significantly associated with ischemia stroke and the A allele increases the risk of being susceptible to this disease in Chinese Han population. That SNP site (rs1 1833579) is not significantly associated with stroke. No significant differences of TNF-α, NGF, IL-6, P-Selectin serum levels are noted between patients under recovery stage and controls. Key words: NINJ2 gene; Polymorphism; single nucleotide; Stroke; Tumor necrosis factor-α; NGF; Interleukin-6; P-Selectin