title: Variation in ITGB3 has sex-specific associations with plasma lipoprotein(a) and whole blood serotonin levels in a population-based sample.
abstract: A recent genome-scan identified the Leu33Pro polymorphism in the beta3 integrin (ITGB3) gene as a quantitative trait locus for whole blood serotonin level in a large Hutterite pedigree. Because both the Leu33Pro polymorphism and the serotonin system have been implicated in cardiovascular disease (CVD) risk and treatment response, we studied additional variation in ITGB3 and its relationship to intermediate phenotypes associated with CVD in the same population. We examined associations between 15 single nucleotide polymorphisms (SNPs) across ITGB3 and five CVD-related traits in the Hutterites: plasma levels of high density lipoprotein-cholesterol (HDL-c), triglycerides (TG), low density lipoprotein-cholesterol (LDL-c), and lipoprotein(a) [Lp(a)] and blood pressure or hypertension. Seven of these SNPs in ITGB3 were associated with whole blood serotonin. Among the intermediate CVD-related phenotypes, only Lp(a) was associated with multiple ITGB3 SNPs, five of which were also associated with serotonin. A sex-stratified analysis revealed that the association between ITGB3 and Lp(a) is present only in females, whereas the association between ITGB3 and serotonin is concentrated in males. Our results suggest that variation in ITGB3 in addition to Leu33Pro could contribute to susceptibility to CVD and serotonin in a sex-specific manner.
authors.affiliation: Department of Human Genetics, The University of Chicago, IL 60637, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Weiss
authors.forename: Mark
authors.initials: M
authors.lastname: Abney
authors.forename: Rodney
authors.initials: R
authors.lastname: Parry
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Scanu
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000235:genetics*; D002648:Child; D005260:Female; D018703:Founder Effect; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics* / Q000502:physiology*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011498:Protein Precursors; D040641:Quantitative Trait Loci; D012701:Serotonin / Q000097:blood*; D012737:Sex Factors; D013023:South Dakota
chemical_list: C061248:ITGB3 protein, human; D039661:Integrin beta3; D008074:Lipoproteins; D011498:Protein Precursors; D012701:Serotonin