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Variation in ITGB3 has sex-specific associations with plasma lipoprotein(a) and whole blood serotonin levels in a population-based sample

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Abstract

A recent genome-scan identified the Leu33Pro polymorphism in the β3 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.

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Acknowledgements

The authors acknowledge Dr. Catherine Bourgain for helpful discussions, Janet Hinman for measurement of lipids, and the Hutterites for their ongoing participation and cooperation in our studies. This work was supported in part by NIH grants HL56399 and HL63533 to C.O., HL62389 to A.M.S., HG02899 and DK55889 to M.A. and a grant from Hoffmann–LaRoche, to C.O.. L.A.W. is supported by an NSF graduate research fellowship.

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Authors and Affiliations

  1. Department of Human Genetics, The University of Chicago, Chicago, IL, 60637, USA

    Lauren A. Weiss, Mark Abney & Carole Ober

  2. School of Medicine, Universityf of South Dakota, Sioux Falls, SD, 57105, USA

    Rodney Parry

  3. Departments of Medicine and Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA

    Angelo M. Scanu

  4. Department of Psychiatry, The University of Chicago, Chicago, IL, 60637, USA

    Edwin H. Cook Jr

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  1. Lauren A. Weiss
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  6. Carole Ober
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Correspondence to Carole Ober.

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Weiss, L.A., Abney, M., Parry, R. et al. Variation in ITGB3 has sex-specific associations with plasma lipoprotein(a) and whole blood serotonin levels in a population-based sample. Hum Genet 117, 81–87 (2005). https://doi.org/10.1007/s00439-004-1250-3

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