Table 4.
Genetic Common Variants and Characteristics of the Studies With Replication or Meta-Analyses Post-2005 That Have Found an Association With IS
| Reference No. | 16 | 16 | 14 | 13 | 21 | 15 | 15 | 15 | 15 |
|---|---|---|---|---|---|---|---|---|---|
| Gene | GP1BA | GP1BA | LTA* | NOS3 | PAI1 | F5 | MTHFR | F2 | ACE |
| Polymorphism | Thr(T)161 met (M) | Kozak variant | 252A> G* | glu298asp | 4G/5G | Arg506GIn | C677T | G20210A | I/D |
| Studies (W) | 6 (3) | 5 (3) | Consortium (6) | Original+replication | Original+meta-analysis (11) | 26 | 22 | 19 | 11 |
| IS | 893 | 1984 | 3550 | 2500 | 4588 | 3387 | 3028 | 2990 | |
| Control | 1313 | 1932 | 6560 | 3500 | 13 798 | 4597 | 7131 | 11 305 | |
| White samples (IS/C) | 358/615 | 2387/5089 | 1417/996 484/751 |
||||||
| Population | Mixed | Mixed | Mixed | European | Mixed | White | White | White | White |
| Analysis for each ethnic group | No | No | Yes | Germany | No | White | White | White | White |
| SNPs | 3 | 3 | 105 | 106 | 1 | 15 | 15 | 15 | 15 |
| P value | 0.004 | 4.54e-0.08 | 0 016 (W) | 0.05+0.04 | 0.002 | 0.001 | 0.002 | 0.006 | <0.001 |
| OR | (M/M versus T/T) 2.08 | (ADD) 1.28 | (ADD) 1.13–1.22 | (4G/4G versus 5G/5G) 0.89 | (DOM) 1.33 | (REC) 1.24 | (DOM) 1.44 | (REC) 1.21 | |
| 95% CI | 0.78–5.54 | 1.12–1.58 | 1.08–1.42 | 1.11–1.86 | 1.08–1.35 | ||||
| Heterogeneity in ORs | Yes | Extreme | Extreme | Yes | No | No | No | ||
| Use of covariates | No | No | Age, sex, HT, SM | Age, sex, Ch, D, HT | No | No | No | No | No |
| Multiple testing correction | FDR in all group | Permutations | |||||||
| Studies confirm association† | No | No | No | No | No | No | No | No | No |
| Studies not showing association‡ | Casas | Casas | Berger | Casas, Lalouschek, Wang | Casas, Lalouschek, Tsantes, Wang | Lalouschek, Wang | Berger, Lalouschek, Wang | Berger, Wang | Berger |
Significant in nonhypertensive IS sample.
Studies cited in references 13–16, 21.
Studies cited in references 17–20.
W indicates white; IS, ischemic stroke; C, control subjects; Ch, cholesterol; HT, hypertension; D, diabetes; SM, smoking; GP1BA, glycoprotein Ib (platelet), alpha polypeptide; LTA, lymphotoxin alpha (tumor necrosis factor superfamily, member 1); NOS3, nitric oxide synthase 3 (endothelial cell); PAI1, plasminogen activator inhibitor type 1; F5, coagulation factor V (proaccelerin, labile factor); MTHFR, 5,10-methylenetetrahydrofolate reductase (NADPH); F2, coagulation factor II (thrombin); ACE, angiotensin I converting enzyme (peptidyl-dipeptidase A) 1.