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A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function.

ABSTRACT: Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 +/- 0.001 log fL; P < 1.08 x 10(-24)) and PLT (per-G effect -4.55 +/- 0.80 10(9)/L; P < 7.19 x 10(-8)) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association with platelet transcript levels for PIK3CG (n = 35; P = .047). The G allele at rs342293 was also associated with decreased binding of annexin V to platelets activated with collagen-related peptide (n = 84; P = .003). The region 7q22.3 identifies the first QTL influencing platelet volume, counts, and function in healthy subjects. Notably, the association signal maps to a chromosome region implicated in myeloid malignancies, indicating this site as an important regulatory site for hematopoiesis. The identification of loci regulating MPV by this and other studies will increase our insight in the processes of megakaryopoiesis and proplatelet formation, and it may aid the identification of genes that are somatically mutated in essential thrombocytosis.

SUBMITTER: Soranzo N

PROVIDER: S-EPMC2714088 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function.

Soranzo Nicole N Rendon Augusto A Gieger Christian C Jones Chris I CI Watkins Nicholas A NA Menzel Stephan S Döring Angela A Stephens Jonathan J Prokisch Holger H Erber Wendy W Potter Simon C SC Bray Sarah L SL Burns Philippa P Jolley Jennifer J Falchi Mario M Kühnel Brigitte B Erdmann Jeanette J Schunkert Heribert H Samani Nilesh J NJ Illig Thomas T Garner Stephen F SF Rankin Angela A Meisinger Christa C Bradley John R JR Thein Swee Lay SL Goodall Alison H AH Spector Tim D TD Deloukas Panos P Ouwehand Willem H WH

Blood 20090212 16

Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 +/- 0.001 log fL; P < 1.08 x 10(-24)) and PLT (per-G effect -4.55 +/- 0.80 10(9)/L; P < 7.19 x 10(-8)) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association wi ...[more]

PMID: 19221038

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Project description:IntroductionSepsis is a public health problem due to its high prevalence and mortality. Mean platelet volume (MPV), a biomarker reported in routine blood counts, has been investigated and shows promise for determining fatal outcomes in septic patients.ObjectiveEvaluate whether the mean platelet volume (MPV) and mean platelet volume-to-platelet count (MPV/P) ratio are predictors of clinical severity and mortality in patients with sepsis.MethodsA prospective population cohort of 163 patients aged 18-97 years was recruited at the Intensive Care Unit of Pablo Arturo Hospital, Quito, Ecuador from 2017-2019 and followed up for 28 days. Patients were diagnosed with sepsis based on SEPSIS-3 septic shock criteria; in which the MPV and the MPV/P ratio were measured on days 1, 2, and 3. Sequential organ failure assessment (SOFA) score and presence of septic shock assessed clinical severity. Mortality on day 28 was considered the fatal outcome.ResultsThe average age of the patients was 61,15 years (SD 20,94) and female sex was predominant. MPV cutoff points at days 1, 2 and 3 were >9,45fL, >8,95fL and >8, 85fL; and (MPV/P) ratio >8, 18, >4, 12 y >3, 95, respectively. MPV at days 2 (9,85fL) and 3 (8,55fL) and (MPV/P) ratio at days 1 (4,42), 2 (4,21), and 3 (8,55), were predictors of clinical severity assessed by septic shock, which reached significance in the ROC curves. MPV and (MPV/P) ratio were also predictors of clinical severity determined by SOFA at days 1, 2, and 3, where higher values were observed in non-survivors reaching significance in all categories. MPV and MPV/P ratio at days 1, 2 and 3 were independent predictor factors of mortality using Cox proportional hazards model (HR 2,31; 95% CI 1,36-3,94), (HR 2,11; 95% CI 1,17-3,82), (HR 2,13; 95% CI 1,07-4,21) and (HR 2,38; 95% CI 1,38-4,12), (HR 2,15; 95% CI 1,14-4,06), (HR 4,43; 95% CI, 1,72-11,37) respectively.ConclusionsMPV and the MPV/P ratio are predictors of clinical severity and mortality in sepsis. The MPV and its coefficient are indicators of the biological behavior of platelets in sepsis. They should be considered as a cost-effective and rapidly available tool that guides the treatment.

Project description:After stenosis of arteriovenous vascular access in hemodialysis patients, platelets play a crucial role in subsequent thrombus formation, leading to access failure. In a previous study, the mean platelet volume (MPV)/platelet count ratio, but not MPV alone, was shown to be an independent predictor of 4-year mortality after myocardial infarction. However, little is known about the potential influence of MPV/platelet count ratio on vascular access patency in hemodialysis patients. A total of 143 patients undergoing routine hemodialysis were recruited between January 2013 and February 2016. Vascular access failure (VAF) was defined as thrombosis or a decrease of greater than 50% of normal vessel diameter, requiring either surgical revision or percutaneous transluminal angioplasty. Cox proportional hazards model analysis ascertained that the change of MPV/platelet count ratio between baseline and 3 months [Δ(MPV/platelet count ratio)3mo-baseline] had prognostic value for VAF. Additionally, the changes of MPV/platelet count ratio over time were compared in patients with and without VAF by using linear mixed model analysis. Of the 143 patients, 38 (26.6%) were diagnosed with VAF. During a median follow-up of 26.9 months (interquartile range 13.0-36.0 months), Δ(MPV/platelet count ratio)3mo-baseline significantly increased in patients with VAF compared to that in patients without VAF [11.6 (6.3-19.0) vs. 0.8 (-1.8-4.0), P< 0.001]. In multivariate analysis, Δ(MPV/platelet ratio count)3mo-baseline was an independent predictor of VAF, after adjusting for age, sex, diabetes, hypertension, coronary artery disease, cerebrovascular disease, vascular access type, the presence of previous VAF, and antiplatelet drug use (hazard ratio, 1.15; 95% confidence interval, 1.10-1.21; P< 0.001). Moreover, a liner mixed model revealed that there was a significant increase of MPV/platelet count ratio over time in patients with VAF compared to those without VAF (P< 0.001). An increase in MPV/platelet count ratio over time was an independent risk factor for VAF. Therefore, continuous monitoring of the MPV/platelet count ratio may be useful to screen the risk of VAF in patients undergoing routine hemodialysis.

Dataset Information

A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function.

Publications

A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function.

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