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Polymorphism in human platelet antigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa), and HPA-5 (GPIa/IIa) was investigated in 329 stroke patients and 444 matched control subjects. HPA genotyping was done by PCR-SSP method. Lower HPA-1a (P < 0.001) and higher HPA-1b (P < 0.001) allele frequencies were seen in patients than control subjects, and homozygosity for HPA-1b (P < 0.001) alleles was more prevalent in stroke cases than in controls. The allele and genotype distributions of the other HPA polymorphic variants were similar between cases and controls. Select HPA combined genotypes comprising the 2121 (Pc 5 0.008) and 2221 (Pc 5 0.018) genotypes, which were positively associated, and the 1111 (Pc < 0.001), which was negatively associated with stroke, thereby conferred a disease susceptibility and protective nature to these genotype combinations. Multivariate analysis confirmed the negative association of the 1111 (P < 0.001) and the positive association of the 2121 (P 5 0.017) combined genotypes with stroke, after adjustment for a number of covariates. This is the first evidence demonstrating differential association of the common 4 HPA gene variants and specific HPA genotype combinations with stroke. Am. J. Hematol. 83:570-573, 2008. V

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A relationship between apolipoprotein E (Apo E) genotype and angiotensin-converting enzyme (ACE) insertion-deletion (Ins-Del) mutation and stroke was suggested. We investigated the association of Apo E4 and ACE Ins/Del genotypes with stroke risk and changes in serum lipids in 228 consecutive Tunisian stroke patients, and 323 age-and gender-matched controls. Comparable frequencies of ACE Ins/Del alleles were seen between patients and controls. The prevalence of Apo epsilon3 allele and Apo E3/E3 were lower (P < 0.001), while the frequency of Apo epsilon4 allele and epsilon4-containing genotypes (E3/E4 and E4/E4) were elevated (P < 0.001) among patients. Higher proportion of Apo E4-carrying + ACE Del/Del positive cases were seen in young (<50 years) patients (P = 0.012), and was associated with large vessel stroke (P = 0.035). Mean serum cholesterol, LDL, HDL, and triglycerides were comparable between E4-containing and no E4-containing and ACE Del/Del-positive patients. Apo E4 and ACE Del/Del genotype combination substantially increase stroke risk, supporting the notion that interactions of multiple gene variants influence stroke pathogenesis.

Polymorphisms in human platelet alloantigen (HPA)-1 and HPA-3 (GPIIb/IIIa), HPA-2 (GPIb/IX), HPA-4 (GPIIIa) and HPA-5 (GPIa/IIa) were investigated in 216 stroke patients and 318 matched control subjects. HPA genotyping was done by the polymerase chain reaction method using sequence-specific primers. Higher frequencies of the HPA-1 a/b (p < 0.001) and HPA-5 a/b (p < 0.001) allele, together with HPA-1 b/b, HPA-5 a/b and HPA-5 b/b genotypes were seen in patients, which was confirmed by regression analysis after controlling for a number of confounding variables. Furthermore, HPA-1 b/b and HPA-5 b/b were significantly associated with the extent of neurological symptoms, and with the recurrence of stroke. Both susceptible (1a/b-2a/a-3a/b-4a/a-5a/b) and protective (1a/a-2a/a-3a/a-4a/a-5a/a; 1a/a-2a/a-3a/b-4a/a-5a/a; 1a/b-2a/a-3a/a-4a/a-5a/a; 1a/b-2a/a-3a/b-4a/a-5a/a) HPA genotypes were identified. This is the first evidence demonstrating differential association of the common 5 HPA gene variants with stroke, with HPA-1b and HPA-5b representing strong genetic risk factors.