TY - JOUR
T1 - Human platelet alloantigens (HPA) 1, HPA2, HPA3, HPA4, and HPA5 polymorphisms in sickle cell anemia patients with vaso-occlusive crisis
AU - Al-Subaie, Abeer M.
AU - Fawaz, Naglaa A.
AU - Mahdi, Najat
AU - Al-Absi, Iman K.
AU - Al-Ola, Khadija
AU - Ameen, Ghada
AU - Almawi, Wassim Y.
PY - 2009/12
Y1 - 2009/12
N2 - Objectives: Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients. Insofar as polymorphism in human platelet alloantigen (HPA) exhibit a prothrombotic nature, we hypothesized that specific HPA polymorphic variants are associated with VOC. We investigated the distribution of HPA1, HPA2, HPA3, HPA4, and HPA5 alleles genotypes among VOC and non-VOC control SCA patients. Patients/methods: This was a case-control study. Study subjects comprised SCA patients with (VOC group; n = 127) or without (Steady-state group; n = 130) VOC events. HPA genotyping was done by PCR-SSP. Results: Significantly higher frequencies of HPA-2b, HPA-3b, and HPA-5b alleles, and marked enrichment of HPA-3b/3b, HPA-5a/5b, and HPA-5b/5b genotypes, were seen in VOC than in control SCA patients. Taking homozygous wild-type genotypes as reference, univariate analysis identified HPA-3a/3b, HPA-3b/3b, and HPA-5b/5b to be associated with VOC. Multivariate analysis confirmed the independent association of only HPA-3a/3b and HPA-3b/3b genotypes with VOC. HPA-3 genotypes were significantly correlated with VOC frequency, type, and medication, and requirement for hospitalization. While both HPA 3a/3b (P = 0.002; OR = 2.94; 95% CI = 1.49-5.77) and 3b/3b (P = 0.006; OR = 3.16; 95% CI = 1.40-7.17) genotypes were associated with need for hospitalization, only HPA-3b/3b was associated with VOC frequency, type (localized vs. generalized), and medication (narcotics vs. NSAIDs). Conclusion: This confirms the association of HPA polymorphisms with SCA VOC, of which HPA-3 appears to be independent genetic risk factors for SCA VOC.
AB - Objectives: Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients. Insofar as polymorphism in human platelet alloantigen (HPA) exhibit a prothrombotic nature, we hypothesized that specific HPA polymorphic variants are associated with VOC. We investigated the distribution of HPA1, HPA2, HPA3, HPA4, and HPA5 alleles genotypes among VOC and non-VOC control SCA patients. Patients/methods: This was a case-control study. Study subjects comprised SCA patients with (VOC group; n = 127) or without (Steady-state group; n = 130) VOC events. HPA genotyping was done by PCR-SSP. Results: Significantly higher frequencies of HPA-2b, HPA-3b, and HPA-5b alleles, and marked enrichment of HPA-3b/3b, HPA-5a/5b, and HPA-5b/5b genotypes, were seen in VOC than in control SCA patients. Taking homozygous wild-type genotypes as reference, univariate analysis identified HPA-3a/3b, HPA-3b/3b, and HPA-5b/5b to be associated with VOC. Multivariate analysis confirmed the independent association of only HPA-3a/3b and HPA-3b/3b genotypes with VOC. HPA-3 genotypes were significantly correlated with VOC frequency, type, and medication, and requirement for hospitalization. While both HPA 3a/3b (P = 0.002; OR = 2.94; 95% CI = 1.49-5.77) and 3b/3b (P = 0.006; OR = 3.16; 95% CI = 1.40-7.17) genotypes were associated with need for hospitalization, only HPA-3b/3b was associated with VOC frequency, type (localized vs. generalized), and medication (narcotics vs. NSAIDs). Conclusion: This confirms the association of HPA polymorphisms with SCA VOC, of which HPA-3 appears to be independent genetic risk factors for SCA VOC.
KW - Human platelet alloantigen
KW - Sickle cell anemia
KW - Vaso-occlusive crisis
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U2 - 10.1111/j.1600-0609.2009.01339.x
DO - 10.1111/j.1600-0609.2009.01339.x
M3 - Article
C2 - 19702628
AN - SCOPUS:70449467284
SN - 0902-4441
VL - 83
SP - 579
EP - 585
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 6
ER -