A Meta-Analysis of Candidate Gene Polymorphisms and Ischemic Stroke in 6 Study Populations

Abstract

patients and 6560 control subjects from 6 case-control association studies conducted in the United States, Europe, and China. Genotyping was performed using the same immobilized probe typing system and meta-analyses were based on summary logistic regressions for each study. The primary analyses were fixed-effects meta-analyses adjusting for age and sex with additive, dominant, and recessive models of inheritance. Results-Although 7 polymorphisms showed a nominal additive association, none remained statistically significant after adjustment for multiple comparisons. In contrast, after stratification for hypertension, 2 lymphotoxin-alpha polymorphisms, which are in strong linkage disequilibrium, were significantly associated among nonhypertensive individuals: LTA 252AϾG (additive model; OR, 1.41 with 95% CI, 1.20 to 1.65; Pϭ0.00002) and LTA 26ThrϾAsn (OR, 1.19 with 95% CI, 1.06 to 1.34; Pϭ0.003). LTA 252AϾG remained significant after adjustment for multiple testing using either the false discovery rate or by permutation testing. The 2 single nucleotide polymorphisms showed no association in hypertensive subjects (eg, LTA 252AϾG, OR, 0.93; 95% CI, 0.84 to 1.03; Pϭ0.17). Conclusions-These

Genetics of stroke

“…Other genetic variations involved in leukotriene biosynthesis, such as the genes encoding LTA4 hydrolase, LTC4 synthase, and the LTB4 receptor, were found to confer an 1059 www.chinaphar.com Guo JM et al Acta Pharmacologica Sinica npg increased risk of ischemic stroke [86,88,89] . However, these associations still need to be confirmed by further studies.…”

The Role of Classic Risk Factors and Prothrombotic Factor Gene Mutations in Ischemic Stroke Risk Development in Young and Middle-Aged Individuals

“…The role of different prothrombotic and proatherogenic polymorphisms in the pathogenesis of ischemic stroke has been investigated [9][10][11][12][13]. Among them, the G20210A polymorphism of the prothrombin gene, the G1691A polymorphism of the factor V gene, the C677T polymorphism of the methylentetrahydrofolate reductase (MTHDR) gene and the 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) are the most frequently studied.…”

Association between ENPP1 K173Q and stroke in a newborn cohort of 395 Brazilian children with sickle cell anemia

“…Furthermore, in a meta-analysis study, PON1 Q192R was found to have no effect on the risk of ischemic stroke in 6 populations of individuals without SCA. 12 In conclusion, using longitudinal analysis, we have shown that the Q genetic variant of the ENPP1 K173Q mutation in children with SCA was associated with an increased risk of stroke and, possibly, with the development of high-risk TCD readings. Contribution: A.R.B.…”