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The rheological and physiological properties of red blood cells (RBCs) are affected by many factors in the vascular environment. Among them, membrane fluctuations (MFs), particularly dynamic fluctuations in RBC cell membrane thickness (RBC-MFs), are likely to be altered by the level of glycation of haemoglobin in patients with diabetes mellitus (DM). We investigated the associations of RBC-MFs with physiological variables associated with DM and cardiovascular diseases (CVDs). Forty-one healthy control subjects and 59 patients with DM were enrolled. Five-microliter samples of blood were collected and diluted 400 times. To measure the RBC-MFs, holotomography was used, which non-invasively and precisely analyses the optical characteristics of RBCs. Associations between the RBC-MFs and biochemical parameters related to glucose homeostasis and lipid profiles were investigated. Independent associations of the RBC-MFs with the presence of CVDs were also analysed. RBC-MFs were lower in patients with DM than in healthy participants (61.64 ± 7.49 nm vs 70.65 ± 6.65 nm, P = 1.4 × 10

The rheological and physiological properties of red blood cells (RBCs) are affected by many factors in the vascular environment. Among them, membrane fluctuations (MFs), particularly dynamic fluctuations in RBC cell membrane thickness (RBC-MFs), are likely to be altered by the level of glycation of haemoglobin in patients with diabetes mellitus (DM). We investigated the associations of RBC-MFs with physiological variables associated with DM and cardiovascular diseases (CVDs). Forty-one healthy control subjects and 59 patients with DM were enrolled. Five-microliter samples of blood were collected and diluted 400 times. To measure the RBC-MFs, holotomography was used, which non-invasively and precisely analyses the optical characteristics of RBCs. Associations between the RBC-MFs and biochemical parameters related to glucose homeostasis and lipid profiles were investigated. Independent associations of the RBC-MFs with the presence of CVDs were also analysed. RBC-MFs were lower in patients with DM than in healthy participants (61.64 ± 7.49 nm vs 70.65 ± 6.65 nm, P = 1.4 × 10−8). RBC-MFs correlated modestly with glycated haemoglobin level (ρ = − 0.47) and weakly with age (ρ = − 0.36), duration of diabetes (ρ = − 0.36), fasting plasma glucose level (ρ = − 0.37), and the 10-year Framingham risk score (ρ = − 0.38) (all P

The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery set and seventy-two patients in the replication set. The patient genomes in the discovery set were sequenced using WES. Also, known tacrolimus pharmacokinetics-related intron variants were genotyped. Tacrolimus C0/D was log-transformed. Sixteen variants were identified including novel CYP3A7 rs12360 and rs10211 by ANOVA. CYP3A7 rs2257401 was found to be the most significant variant among the periods by ANOVA. Seven variants including CYP3A7 rs2257401, rs12360, and rs10211 were analyzed by SNaPshot in the replication set and the effects on tacrolimus C0/D were verified. A linear mixed model (LMM) was further performed to account for the effects of the variants and clinical factors. The combined set LMM showed that only CYP3A7 rs2257401 was associated with tacrolimus C0/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C0/D in those expressing CYP3A5, showing its own effect. The results suggest that CYP3A7 rs2257401 may serve as a significant genetic marker for tacrolimus pharmacokinetics in kidney transplantation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.