Piezo1 plays a role in erythrocyte volume homeostasis.

Mechanosensitivity is an inherent property of virtually all cell types, allowing them to sense and respond to physical environmental stimuli. Stretch-activated ion channels represent a class of mechanosensitive proteins which allow cells to respond rapidly to changes in membrane tension; however their identity has remained elusive. The piezo genes have recently been identified as a family of stretch-activated mechanosensitive ion channels. We set out to determine the role of piezo1 during zebrafish development. Here we report that morpholino-mediated knockdown of piezo1 impairs erythrocyte survival without affecting hematopoiesis or differentiation. Our results demonstrate that piezo1 is involved in erythrocyte volume homeostasis, disruption of which results in swelling/lysis of red blood cells and consequent anemia.

The impact of vitamin D receptor genotype on the management of anemia in hemodialysis patients.

BACKGROUND: Both in vitro and in vivo studies have shown that calcitriol, the active form of vitamin D, is involved in hematopoiesis. We hypothesized that the vitamin D receptor (VDR) genotype, which may differentiate response to endogenous or exogenous active vitamin D, has a role in the management of anemia in hemodialysis (HD) patients. METHODS: The VDR BsmI gene polymorphism was determined in 91 HD patients and 85 healthy controls. In addition to well-known factors responsible for both anemia and inadequate response to erythropoietin (EPO), we examined the contribution of the VDR genotype to hematocrit (Hct), hemoglobin (Hb) level, total weekly dose of EPO, and EPO-Hb ratio as an index of patient EPO need. RESULTS: Genotype distributions for the VDR gene were under the Hardy-Weinberg equilibrium and similar in patients and controls (genotypes BB, Bb, and bb: 22.0%, 38.5%, and 39.5% in patients versus 24.7%, 48.2%, and 27.1% in controls). There were statistically significant differences in Hct, Hb level, EPO dose, and EPO-Hb ratio in patients with the three BsmI genotypes, whereas the other parameters were the same. Comparison of patients with an Hb level less than versus greater than 11 g/dL showed that the former patients had lower albumin levels (P = 0.001), higher C-reactive protein levels (P = 0.014), and a greater frequency of BB genotype (P < 0.001). Similarly, comparison of patients with an EPO-Hb ratio in the highest quartile versus those in the lowest quartile showed that the former patients had lower albumin and transferrin levels (P = 0.013 for both) and greater frequencies of BB genotype (P = 0.016). In logistic regression analysis, both BB genotype and low serum albumin level were found to be the only independent predictors for an Hb level less than 11 g/dL (P < 0.001 and P = 0.046, respectively). Both parameters also predicted being in the highest quartile of EPO-Hb ratio (P = 0.004 for both). CONCLUSION: The VDR BsmI gene polymorphism may predict both Hb level and EPO need in HD patients. However, because the underlying mechanisms have not been clarified in the present study, further research on this issue is needed.

The relation between erythrocyte volume and folate levels is influenced by a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T).

BACKGROUND: The enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and folate-dependent reactions. Homozygosity for a common polymorphism in the MTHFR gene (C677T, Ala to Val) is associated with an increased risk of neural tube defects and hyperhomocysteinemia in individuals with low folate levels. Homozygous carriers of the polymorphism with adequate folate levels, on the other hand, seem to be at lower risk for colorectal cancer. Homozygous carriers of the polymorphism (5-15% of the white population) probably represent a subpopulation with increased folate needs. Hematological sequelae of folate deficiency have been recognized for a long time. However, no data exist concerning the relation between the C677T MTHFR polymorphism, folate levels, and hematological parameters. METHODS: We investigated associations between the C677T MTHFR polymorphism, folate levels, total plasma homocysteine, and hematological parameters in 94 patients with cerebrovascular disease (transient ischemic attack/minor stroke) and in 82 healthy subjects. RESULTS: Homozygous carriers (VV) of the polymorphism with low folate levels showed significantly higher homocysteine levels than mutation-negative (AA) and heterozygous (AV) subjects (P = 0.038). Furthermore, VV subjects in the lowest folate quartile exhibited significantly higher mean erythrocyte volumes (MCV) and a tendency towards higher erythrocyte hemoglobin content (MCH) than AA and AV subjects (P = 0.008 and 0.069, respectively). Although MCV was not influenced by folate levels in AA and AV subjects, in VV subjects a significant inverse correlation with folate levels could be demonstrated (P = 0.544 and 0.020, respectively). CONCLUSION: We demonstrate an association between the C677T polymorphism, folate levels, and hematological parameters. The elevation of MCV in homozygous carriers of the polymorphism with low folate levels indicates impaired DNA synthesis and/or methylation in these subjects. Considering our data and the results of previous studies, the polymorphism may have contrary effects on homocysteine metabolism and DNA synthesis/methylation dependent on a subject's folate supply. Although the polymorphism is disadvantageous in homozygous carriers with low folate levels, its presence may be beneficial in individuals with adequate folate supply.