title: Genetic variability of platelet glycoprotein Ibalpha gene.
abstract: Platelet membrane glycoprotein (GP) Ibalpha is a critical component of platelet adhesion complex to subendothelium structures following tissue injury or pathological surfaces, such as atherosclerotic plaques. Polymorphisms of the GPIbalpha gene have been associated with a high risk for occlusive vascular disease, and its distribution varies considerably among distinct populations. These polymorphisms comprise the human platelet antigen (HPA)-2 system, the -5C/T dimorphism of the Kozak sequence, and the variable number of tandem 39-bp repeats (VNTR). Here we report the prevalence of the GPIbalpha gene polymorphisms among Brazilians, a highly ethnically diverse population. We analyzed 492 subjects of European, African, or Indigenous origin. It was possible to determine ten distinct haplotypes. The most common ( reverse similar 40%) haplotype was the Kozak-TT/HPA-2aa/VNTR-CC for both Caucasian and African descent. However, among Indigenous, Kozak-TT/HPA-2aa/VNTR-CC and Kozak-TC/HPA-2aa/VNTR-CC were equally present. Although a strong linkage disequilibrium between VNTR and HPA-2 polymorphism had also been observed, here we determined incomplete linkage disequilibrium in 10% of subjects from all ethnic groups. VNTR-E, a rare variant lacking the 39-bp repeat, was identified in two unrelated subjects, and functional platelet studies revealed no abnormalities. The VNTR-A allele, the largest variant containing four copies of the repeats, was not identified in this population. However, homozygosity for the VNTR-A allele (Kozak-TT/HPA-2aa/VNTR-AA) was determined in two distinct species of nonhuman primates. These results suggest a greater complex evolutionary mechanism in the macroglycoprotein region of the GPIbalpha gene and may be useful in the design of gene-disease association studies for vascular disease.
authors.affiliation: Hematology and Hemotherapy Center, State University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Margareth C
authors.initials: MC
authors.lastname: Ozelo
authors.forename: Devanira S P
authors.initials: DS
authors.lastname: Costa
authors.forename: Lucia H
authors.initials: LH
authors.lastname: Siqueira
authors.forename: Tania M F
authors.initials: TM
authors.lastname: Machado
authors.forename: Vagner
authors.initials: V
authors.lastname: Castro
authors.forename: Marilda S
authors.initials: MS
authors.lastname: Gonçalves
authors.forename: Raimundo C
authors.initials: RC
authors.lastname: Menezes
authors.forename: Manoel
authors.initials: M
authors.lastname: Soares
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Costa
authors.forename: Valder R
authors.initials: VR
authors.lastname: Arruda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D044383:Black People / Q000235:genetics*; D001938:Brazil; D005260:Female; D006239:Haplotypes; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D007199:Indians, South American / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020080:Tandem Repeat Sequences / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex