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

TY - JOUR

T1 - Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study

AU - Panova-Noeva, Marina

AU - Schulz, Andreas

AU - Hermanns, M Iris

AU - Grossmann, Vera

AU - Pefani, Evgenia

AU - Spronk, Henri M H

AU - Laubert-Reh, Dagmar

AU - Binder, Harald

AU - Beutel, Manfred

AU - Pfeiffer, Norbert

AU - Blankenberg, Stefan

AU - Zeller, Tanja

AU - Münzel, Thomas

AU - Lackner, Karl J

AU - Ten Cate, Hugo

AU - Wild, Philipp S

N1 - © 2016 by The American Society of Hematology.

PY - 2016/1/14

Y1 - 2016/1/14

N2 - 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.

AB - 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.

KW - Age Factors

KW - Aged

KW - Cardiovascular Diseases/blood

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Male

KW - Mean Platelet Volume/statistics & numerical data

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Sex Factors

KW - Thrombosis/blood

U2 - 10.1182/blood-2015-07-660308

DO - 10.1182/blood-2015-07-660308

M3 - SCORING: Journal article

C2 - 26518434

VL - 127

SP - 251

EP - 259

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 2

ER -