Association of toll-like receptor 2 polymorphisms with National Institute of Health Stroke Scale scores of ischemic stroke patients.
ABSTRACT Toll-like receptor 2 (TLR2) has been shown to have an important role in the postischemic inflammatory response and to contribute to ischemic brain damage. In this study, we investigated whether coding region single nucleotide polymorphisms (SNPs) of the TLR2 gene were associated with ischemic stroke (IS) and with clinical phenotypes in IS patients. We genotyped two SNPs (rs3804099 [Asn199Asn] and rs3804100 [Ser450Ser]) using direct sequencing in 202 IS patients and 291 control subjects. No SNPs of the TLR2 gene were found to be associated with IS. However, in analysis of clinical phenotypes, we found that rs3804099 was associated with the National Institute of Health Stroke Scale (NIHSS) scores of IS patients in codominant (TC vs. TT, p = 0.0005; CC vs. TT, p = 0.0007) and dominant models (TC/CC vs. TT, p = 0.0001). Also, rs3804100 revealed significant association in codominant (TC vs. TT, p = 0.0002; CC vs. TT, p = 0.008) and dominant models (TC/CC vs. TT, p < 0.0001). In allele frequency analysis, we also found that the C alleles of rs3804099 and rs3804100 were associated with higher NIHSS scores (p = 0.0003 in rs3804099; p = 0.0001 in rs3804100). Our results suggest that TLR2 may be related to severe IS.
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ABSTRACT: Neuronal expression of ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) has been demonstrated after brain ischemia. To investigate whether ABCB1 polymorphisms are associated with the development, risk factors (hypertension, dyslipidemia, and diabetes mellitus), severity (National Institutes of Health Stroke Scale, NIHSS), and sequelae (Modified Barthel Index, MBI) of ischemic stroke (IS), four single nucleotide polymorphisms (SNPs) of the ABCB1 gene [rs4148727, promoter, -154T>C; rs3213619, 5'-untranslation region (5'UTR), -129T>C); rs1128503, synonymous, Gly412 (C>T); rs3842, 3'UTR, A>G] were analyzed in 121 IS patients and 291 control subjects. SNPStats and SPSS 18.0 were used to obtain odds ratios (OR), 95% confidence intervals (CI), and p values. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, and log-additive models) were applied to analyze the genetic data. The rs3842 SNP was weakly associated with the development of IS (p=0.020 in codominant1 model and p=0.028 in dominant model). In the analysis of clinical phenotypes, ABCB1 polymorphisms were nominally associated with hypertension (rs3213619 and rs3842, p<0.05), dyslipidemia (rs1128503, p<0.05), diabetes (rs3842, p<0.05), and NIHSS (rs4148727, p<0.05). Interestingly, rs3842 showed statistically strong association between IS with hypertension and IS without hypertension (Fisher's exact p=0.003, OR=0.11, 95% CI=0.03-0.51 in recessive model). These results suggest that the ABCB1 gene may be associated with the development and clinical phenotypes of IS in Korean population.Experimental neurobiology. 12/2012; 21(4):164-71.