Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets
Extracellular vesicles (EVs) mediate cell interactions in biological processes, such as receptor activation or molecule transfer. Estimates of variation by age and sex have been limited by small sample size, and no report has assessed the contribution of genetic factors to levels of EVs. Here, we ev...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7183 |
| _version_ | 1797605173712912384 |
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| author | Valeria Orrù Francesca Virdis Michele Marongiu Valentina Serra David Schlessinger Marcella Devoto Francesco Cucca Edoardo Fiorillo |
| author_facet | Valeria Orrù Francesca Virdis Michele Marongiu Valentina Serra David Schlessinger Marcella Devoto Francesco Cucca Edoardo Fiorillo |
| author_sort | Valeria Orrù |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) mediate cell interactions in biological processes, such as receptor activation or molecule transfer. Estimates of variation by age and sex have been limited by small sample size, and no report has assessed the contribution of genetic factors to levels of EVs. Here, we evaluated blood levels of 25 EV and 3 platelet traits in 974 individuals (933 genotyped) and reported the first genome-wide association study (GWAS) on levels of these traits. EV levels all decreased with age, whereas the trend for their surface markers was more heterogeneous. Platelets and CD31dim platelet EVs significantly increased in females compared to males, although CD31 expression on both platelets and platelet EVs decreased in females. Levels of the other EV subsets were similar between sexes. GWAS revealed three statistically significant genetic signals associated with EV levels in the <i>F10</i> and <i>GBP1</i> genes and in the intergenic region between <i>LRIG1</i> and <i>KBTBD8</i>. These add to a signal in the 3′UTR of <i>RHOF</i> associated with CD31 expression on platelets that was previously found to be associated with other platelet traits. These findings suggest that EV formation is not a simple, constant adjunct of metabolism but is under both age-related and genetic control that can be independent of the regulation of the levels of the cells from which the EVs derive. |
| first_indexed | 2024-03-11T04:57:22Z |
| format | Article |
| id | doaj.art-a69b303fda604ae691e5b65ebcf52455 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:57:22Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a69b303fda604ae691e5b65ebcf524552023-11-17T19:36:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248718310.3390/ijms24087183Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and PlateletsValeria Orrù0Francesca Virdis1Michele Marongiu2Valentina Serra3David Schlessinger4Marcella Devoto5Francesco Cucca6Edoardo Fiorillo7Institute for Genetic and Biomedical Research, National Research Council (CNR), 08045 Lanusei, ItalyInstitute for Genetic and Biomedical Research, National Research Council (CNR), 08045 Lanusei, ItalyInstitute for Genetic and Biomedical Research, National Research Council (CNR), 08045 Lanusei, ItalyInstitute for Genetic and Biomedical Research, National Research Council (CNR), 08045 Lanusei, ItalyLaboratory of Genetics and Genomics, National Institute on Ageing, National Institutes of Health, Baltimore, MD 21224, USAInstitute for Genetic and Biomedical Research, National Research Council (CNR), 09042 Monserrato, ItalyInstitute for Genetic and Biomedical Research, National Research Council (CNR), 08045 Lanusei, ItalyInstitute for Genetic and Biomedical Research, National Research Council (CNR), 08045 Lanusei, ItalyExtracellular vesicles (EVs) mediate cell interactions in biological processes, such as receptor activation or molecule transfer. Estimates of variation by age and sex have been limited by small sample size, and no report has assessed the contribution of genetic factors to levels of EVs. Here, we evaluated blood levels of 25 EV and 3 platelet traits in 974 individuals (933 genotyped) and reported the first genome-wide association study (GWAS) on levels of these traits. EV levels all decreased with age, whereas the trend for their surface markers was more heterogeneous. Platelets and CD31dim platelet EVs significantly increased in females compared to males, although CD31 expression on both platelets and platelet EVs decreased in females. Levels of the other EV subsets were similar between sexes. GWAS revealed three statistically significant genetic signals associated with EV levels in the <i>F10</i> and <i>GBP1</i> genes and in the intergenic region between <i>LRIG1</i> and <i>KBTBD8</i>. These add to a signal in the 3′UTR of <i>RHOF</i> associated with CD31 expression on platelets that was previously found to be associated with other platelet traits. These findings suggest that EV formation is not a simple, constant adjunct of metabolism but is under both age-related and genetic control that can be independent of the regulation of the levels of the cells from which the EVs derive.https://www.mdpi.com/1422-0067/24/8/7183extracellular vesiclesflow cytometryGWAS |
| spellingShingle | Valeria Orrù Francesca Virdis Michele Marongiu Valentina Serra David Schlessinger Marcella Devoto Francesco Cucca Edoardo Fiorillo Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets International Journal of Molecular Sciences extracellular vesicles flow cytometry GWAS |
| title | Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets |
| title_full | Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets |
| title_fullStr | Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets |
| title_full_unstemmed | Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets |
| title_short | Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets |
| title_sort | effect of genetic factors age and sex on levels of circulating extracellular vesicles and platelets |
| topic | extracellular vesicles flow cytometry GWAS |
| url | https://www.mdpi.com/1422-0067/24/8/7183 |
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