title: Protein Z polymorphisms associated with vaso-occlusive crisis in young sickle cell disease patients.
abstract: We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) vaso-occlusive crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P=0.03), rs3024719 (P=0.02), rs3024731 (P<0.001), and rs3024735 (P<0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P=0.028) and rs3024735 (P=0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P=0.024), AGAA (P=0.011), and GGTG (P=0.002), and reduced frequency of AGTG haplotype (P=0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (P(c)=0.001) and GGTG (P(c)=0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.
authors.affiliation: Department of Pediatrics, Salmaniya Medical Complex, Manama, Bahrain.
authors.forename: Najat
authors.initials: N
authors.lastname: Mahdi
authors.forename: Tala M
authors.initials: TM
authors.lastname: Abu-Hijleh
authors.forename: Farah M
authors.initials: FM
authors.lastname: Abu-Hijleh
authors.forename: Mai S
authors.initials: MS
authors.lastname: Sater
authors.forename: Khadija
authors.initials: K
authors.lastname: Al-Ola
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000150:complications / Q000235:genetics*; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000235:genetics*; D001798:Blood Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000502:physiology; D014652:Vascular Diseases / Q000150:complications / Q000235:genetics; D055815:Young Adult
chemical_list: D001798:Blood Proteins; C026080:plasma protein Z