title: Polymorphisms in glycoprotein (GP) lb alpha are not associated with adverse outcomes in primigravidae.
abstract: The platelet glycoprotein lb-IX complex is critical in platelet adhesion under conditions of high shear stress. Three genetic polymorphisms in the GPlbalpha subunit have been variably associated with thrombotic disorders. Women with serious obstetrical complications have an increased incidence of polymorphisms in other coagulation factors predisposing them alpha to thrombosis. Three GPlb variants were genotyped in 271 women in an Irish primigravid population, 258 with recorded outcomes, and in 22 patients with recurrent thrombosis and 15 patients with recurrent fetal loss. These were: the 13 amino acid variable number of tandem repeats (VNTR A/B/C/D), the Thr145Met antigen (HPA2) and a variant in the 'Kozak' sequence 5 bases upstream of the methionine initiation codon (T-5C). The VNTR B and HPA2b (145Met) alleles were strongly associated with each other, as found in previous analyses of Caucasian populations (estimated haplotype frequency 5%). The Kozak rarer C variant was found at an allele frequency of 9.1%, and appeared completely associated with the commonest haplotype of the other markers (VNTR/C, 145Thr). GPlb alpha genotype did not have any marked influence on pregnancy outcome. The Kozak/C variant was not significantly elevated in the 15 primigravidae patients who miscarried compared with 233 normal outcomes (OR=2.09, CI=0.7-6.4), neither was the 145Met variant (P =0.38). The Kozak/C variant was not elevated in the six primigravidae patients who developed pre-eclampsia (OR=0.84, CI=0.1-7.3). Comparison of the 271 primigravidae with 15 recurrent fetal loss patients showed no association between Kozak/C and recurrent fetal loss (OR=0.65, CI=0.1-3.0), nor with the 145Met variant (OR=0.62, CI=0.1-4.9). Combining miscarriage cases, recurrent thrombosis cases, pre-eclampsia, and intrauterine growth retardation outcome groups together, there is still no significant genotypic difference compared with normal outcome (OR=0.90, CI=0.4-1.9). Genetic variants of GPlbalpha are unlikely to contribute to adverse events associated with thrombosis in a primigravidae population.
authors.affiliation: Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin.
authors.forename: A
authors.initials: A
authors.lastname: Hillmann
authors.forename: D C
authors.initials: DC
authors.lastname: Shields
authors.forename: D J
authors.initials: DJ
authors.lastname: Fitzgerald
authors.forename: D
authors.initials: D
authors.lastname: Kenny