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

Abstract

Key Points• 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. 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. (Blood. 2016;127(2):251-259)

Mean Platelet Volume and Arterial Stiffness – Clinical Relationship and Common Genetic Variability

“…Since, MPV has been also shown to be associated with increased risk of arterial and venous thrombosis and recent studies indicate that MPV is significantly determined by traditional CVRFs and a higher MPV goes along with a higher risk of death17, it is tempting to conclude that increased MPV may adversely affect vascular function (stiffness) mainly because of its functional “side effects”.…”

“…Coefficients of variation for MPV range between 0.8 and 2.2% over time with a mean of 1.4%. Details of internal quality control for Advia 120 hematology systems and validation for inter-instrument variation for MPV measurements have been published earlier17. Biochemical analysis of blood glucose and C-reactive protein measured in plasma and total cholesterol, high density lipoprotein (HDL), and triglycerides measured in serum were determined within 1 hour after sampling by routine methods.…”

“…After quality control, genetic data were available for analysis in 4,175 individuals. The methodology for genotyping has been described before17.…”

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

“…62 There are known sex differences in cell counts, with females consistently having higher PLT and mixed results on MPV. 63,64 Similar to well-established PLT-and MPV-associated transcriptional regulator JMJD1C, ZMIZ2 directly interacts with AR to modulate AR-mediated transcription and influences mesodermal development, and thus genetic variation in ZMIZ2 could potentially contribute to hormonally mediate differences in PLT across genders. [65][66][67] Also associated with increased PLT and decreased RBC indices was rs55707100 in MAP1A.…”

“…Loos, 13 Albert Vernon Smith, 59,60 Tamara B. Harris, 61 Lenore J. Launer, 61 Vilmundur Gudnason, 59,60 Digna R. Velez Edwards, 62 Eric S. Torstenson, 19 Yongmei Liu, 63 Russell P. Tracy, 64 Jerome I. Rotter, 65,66 Stephen S. Rich, 22 Heather M. Highland, 67,68 Eric Boerwinkle, 18,69 Jin Li, 70 Ethan Lange, 21,71 James G. Wilson, 72 Evelin Mihailov, 73 Reedik Mägi, 73 Joel Hirschhorn, 7,74 Andres Metspalu, 73 Tõnu Esko, 7,73 Caterina Vacchi-Suzzi, 75 Mike A. Nalls, 76 Alan B. Zonderman, 12 Michele K. Evans, 12 Gunnar Engström, 77,78 Marju Orho-Melander, 77 We thank all participants and study coordinating centers. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the NIH, or the U.S. Department of Health and Human Services.…”