Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study

• Published in: Blood 2016-01, Vol.127 (2), p.251-259
• Main Authors: Panova-Noeva, Marina, Schulz, Andreas, Hermanns, M. Iris, Grossmann, Vera, Pefani, Evgenia, Spronk, Henri M.H., Laubert-Reh, Dagmar, Binder, Harald, Beutel, Manfred, Pfeiffer, Norbert, Blankenberg, Stefan, Zeller, Tanja, Münzel, Thomas, Lackner, Karl J., ten Cate, Hugo, Wild, Philipp S.
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Female; Genetic Predisposition to Disease; Humans; Male; Mean Platelet Volume - statistics & numerical data; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Sex Factors; Thrombosis - blood; Thrombosis - epidemiology; Thrombosis - genetics
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2015-07-660308

Mean platelet volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive analysis including known genetic and nongenetic factors that determine MPV is still lacking. MPV has been evaluated in 15 010 individuals from the population-based Gutenberg Health Study. Genetic information was available for 4175 individuals. Our results showed that age (β, 0.0346; 95% confidence interval [CI], 0.0255 to 0.0436), cardiovascular risk factors (CVRFs) such as smoking (β, 0.178; 95% CI, 0.128 to 0.229), hypertension (β, 0.05; 95% CI, 0.00289 to .0981), and high glucose level (β, 0.00179; 95% CI, 0.0006 to 0.00299) were linked with higher MPV in males only. Intake of oral contraceptives (β, 0.150; 95% CI, 0.0649 to 0.236) and menstruation (β, 0.123; 95% CI, 0.0231 to 0.224) were strongly associated with higher MPV in females. Seven single nucleotide polymorphisms (SNPs) for females and 4 SNPs for males were associated with higher MPV. The full model, including age, CVRFs, laboratory parameters, medications, and genetic variation, explained 20.4% of the MPV variance in females and 18.6% in males. The curves of cumulative mortality, stratified for sex, showed worse survival for males only with MPV >9.96 fL vs MPV ≤9.96 fL (P < .0001). This study provides evidence for heterogeneity in the profile of determinants for MPV between sexes. The observed interactions between genetic variability, CVRFs, and MPV and its association with the development of cardiovascular disease or thrombotic risk need to be further investigated. •Genetic and nongenetic determiners of MPV substantially differ between males and females in a large population-based study.•MPV in males is significantly determined by the traditional CVRFs, and males with higher MPV are at higher risk of death.