title: Human platelet alloantigens (HPA) 1, HPA2, HPA3, HPA4, and HPA5 polymorphisms in sickle cell anemia patients with vaso-occlusive crisis.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  This confirms the association of HPA polymorphisms with SCA VOC, of which HPA-3 appears to be independent genetic risk factors for SCA VOC.
authors.affiliation: Department of Medical Biochemistry, Arabian Gulf University, Manama, Bahrain.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Al-Subaie
authors.forename: Naglaa A
authors.initials: NA
authors.lastname: Fawaz
authors.forename: Najat
authors.initials: N
authors.lastname: Mahdi
authors.forename: Iman K
authors.initials: IK
authors.lastname: Al-Absi
authors.forename: Khadija
authors.initials: K
authors.lastname: Al-Ola
authors.forename: Ghada
authors.initials: G
authors.lastname: Ameen
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D056586:Acute Chest Syndrome / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000235:genetics*; D016824:Antigens, Human Platelet / Q000235:genetics*; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics*; D001445:Bahrain / Q000453:epidemiology; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D010146:Pain / Q000209:etiology; D010973:Platelet Adhesiveness; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics*
chemical_list: C044561:3a alloantigen, human; C083448:3b alloantigen, human; D016824:Antigens, Human Platelet