Background: HSD3B1 and HSD3B2 are crucial enzymes for the synthesis of hormonal steroids, including aldosterone. Therefore, HSD3B gene variations could possibly influence blood pressure (BP) by affecting the aldosterone level. Methods: We performed a haplotype-and diplotype-based case-control study to investigate the association between the HSD3B gene variations and essential hypertension (EH), aldosterone level, and left ventricular hypertrophy (LVH). A total of 275 EH patients and 286 controls were genotyped for four SNPs of the HSD3B1 gene (rs3765945, rs3088283, rs6203, and rs1047303) and for two SNPs of the HSD3B2 gene (rs2854964 and rs1819698). Aldosterone and LVH were investigated in 240 and 110 subjects respectively. Results: Significant differences were noted for the total and the male subject groups for the recessive model (CC versus TCCTT) of rs6203 between the controls and EH patients (PZ0.030 and PZ0.008 respectively). The frequency of the T-C haplotype established by rs3088283-rs1047303 was significantly higher for EH patients compared with the controls (PZ0.014). Even though the polymorphism of HSB3B1 was not associated with LVH, the diplotype established by rs3088283-rs1047303 in the total subject group, along with the systolic BP, diastolic BP, and aldosterone level were significantly higher for those subjects who had the T-C haplotype versus those who did not (PZ0.025, PZ0.014, and PZ0.006 respectively). Conclusion: rs6203 and rs1047303 in the HSD3B1 gene are useful genetic markers for EH, while polymorphisms of HSD3B1 are associated with the BP and aldosterone level.

ObjectiveWe aimed to clarify the onset of diabetes.DesignData from 27,392 nondiabetic health examinees were retrospectively analyzed for a mean of 5.3 years. Trajectories of fasting plasma glucose (FPG), body mass index (BMI), and the single point insulin sensitivity (Si) estimator (SPISE), an index of Si, 10 years before diagnosis of prediabetes (PDM; n = 4781) or diabetes (n = 1061) were separately assessed by a mixed effects model. Diabetes and PDM were diagnosed by the American Diabetes Association definition on the basis of FPG and glycosylated hemoglobin A1c values.ResultsIn individuals who developed diabetes, mean FPG and BMI were significantly higher (P < 0.01 each) and SPISE lower than those who did not at −10 years: FPG 101.5 mg/dL vs 94.5 mg/dL, BMI 24.0 kg/m2 vs 22.7 kg/m2, and SPISE 7.32 vs 8.34, P < 0.01 each. These measurements, in subjects who developed prediabetes, were slightly but definitely different from those who did not, already at −10 years: FPG 91.8 mg/dL vs 89.6 mg/dL, BMI 22.6 kg/m2 vs 22.1 kg/m2, and SPISE 8.44 vs 8.82, P < 0.01 each. In both cases, the differences were progressively greater toward year 0, the time of diabetes, or PDM diagnosis.ConclusionsFPG was significantly elevated in those who developed diabetes at least 10 years before diagnosis of diabetes, and this was also the case in those who developed PDM. Glucose dysregulation precedes diagnosis of diabetes at least for 20 years.

BackgroundPrediabetes is an independent risk factor for cardiovascular diseases. Mean platelet volume (MPV) can reflect platelet activity, and high MPV is associated with thrombogenic activation and an increased risk of cardiovascular disease. In diabetic patients, MPV is higher when compared with normal subjects. However, the relationship between MPV and prediabetes is poorly understood. The purpose of the present study was to compare MPV in prediabetic and normoglycemic subjects, and to evaluate the relationship between MPV and fasting plasma glucose (FPG) levels in these two groups.MethodsWe retrospectively studied 1876 Japanese subjects who had undergone health checks at Iida Municipal Hospital. Age, sex, body mass index (BMI), blood pressure, medical history, smoking habits, alcohol intake, lipid profiles, FPG levels, and MPV were evaluated. Subjects were categorized into four groups according to FPG: Q1 (70 mg/dL ≤ FPG < 90 mg/dL, n = 467), Q2 (90 mg/dL ≤ FPG < 95 mg/dl, n = 457), Q3 (95 mg/dL ≤ FPG < 100 mg/dL, n = 442), and Q4 (100 mg/dL ≤ FPG < 126 mg/dL, n = 512). Q1, Q2, and Q3 were defined as normal FPG groups and Q4 was defined as prediabetic group.ResultsThe MPV increased with the increasing FPG levels, in the following order: Q1 (9.89 ± 0.68 fl), Q2 (9.97 ± 0.69 fl), Q3 (10.02 ± 0.72 fl), and Q4 (10.12 ± 0.69 fl). After adjusting for the confounding parameters, MPV of the prediabetic group was higher than that in other groups (P < 0.001 for Q4 vs. Q1 and Q2, and P < 0.05 for Q4 vs. Q3). MPV in the high-normal glucose group (Q3) was significantly higher than in the low-normal glucose group (Q1). MPV was independently and positively associated with FPG, not only in prediabetic subjects but also in normal FPG subjects (β = 0.020 and β = 0.006, respectively).ConclusionsMPV in patients with prediabetes was higher than that in normal subjects, and was positively associated with FPG levels in prediabetic and normal subjects.

Hypertension in pregnancy is a multifactorial disorder caused by a complex combination of environmental factors and several predisposing genes. Since estrogen modulates placental vascular development, estrogen synthases are considered plausible candidate genes. The aim of this haplotype-based case-control study was to estimate whether polymorphisms of the maternal estrogen synthesis genes (CYP19A1, HSD3B1 and HSD3B2) are associated with preeclampsia (PE) and gestational hypertension (GH). To examine the genetic markers in 69 PE and 62 GH patients and in 155 age-matched, primiparous, healthy control subjects, genotyping of 5 SNPs for the CYP19A1 gene (rs1870049, rs936306, rs700518, rs700519, and rs4646), 3 SNPs for the HSD3B1 gene (rs3765945, rs6203, and rs1047303), and 2 SNPs for the HSD3B2 gene (rs2854964 and rs1819698) was performed. For rs700158 of CYP19A1, the frequencies of the AG+GG genotype and the G allele were significantly higher in PE as compared to controls (P = 0.037, P = 0.033, respectively). Logistic regression analyses indicated that the AG+GG genotype of rs700158 was a PE risk factor (odds ratio = 2.15, P = 0.026). In addition, the frequency of the G-G haplotype established by rs700518-rs4646 was also significantly higher for PE (P = 0.017). These data suggest that the estrogen synthesis gene, CYP19A1 is associated with PE in the Japanese population.

Background: As aromatase-deficient mice, which are deficient in estrogens, reportedly have reduced blood pressure, the aromatase gene (CYP19A1) is thought to be a susceptibility gene for essential hypertension (EH). The aim of the present study was to investigate the relationship between CYP19A1 and EH by examining single nucleotide polymorphisms (SNPs).Methods: Five SNPs in the human CYP19A1 gene (rs1870049, rs936306, rs700518, rs10046 and rs4646) were selected, and an association study was performed in 218 Japanese EH patients and 225 age-matched normotensive (NT) individuals.Results: There were significant differences between these groups in the distribution of genotypes rs700518 and rs10046 in male subjects, and genotypes rs700518, rs10046 and rs4646 in female subjects. On multiple logistic regression analysis, a significant association between rs700518 (p=0.023) and rs10046 (p=0.036) in male subjects and rs700518 in female subjects (p=0.018) was noted. Interestingly, the risk genotypes of rs700518 and rs10046 showed a sex-dependent inverse relationship. Both SBP and DBP levels were higher in total (cases and controls) male subjects with the G/G genotype with rs700518 or the T/T genotype with rs10046 than in male subjects without the G/G genotype or T/T genotype. SBP levels were lower in female subjects with the G/G genotype with rs700518 than in female subjects without G/G. The A-T haplotype constructed with rs1870049 and rs10046 was a susceptibility marker for EH.Conclusions: We confirmed that rs700518 and rs10046, as well as a haplotype constructed with rs1870049 and rs10046, in the human CYP19A1 gene can be used as genetic markers for gender-specific EH.

The aim of this study was to evaluate the utility of hemoglobin A1c (HbA1c) to identify individuals with diabetes and prediabetes in the Japanese population. A total of 1372 individuals without known diabetes were selected for this study. A 75 g oral glucose tolerance test (OGTT) was used to diagnose diabetes and prediabetes. The ability of HbA1c to detect diabetes and prediabetes was investigated using receiver operating characteristic (ROC) analysis. The kappa (κ) coefficient was used to test the agreement between HbA1c categorization and OGTT-based diagnosis. ROC analysis demonstrated that HbA1c was a good test to identify diabetes and prediabetes, with areas under the curve of 0.918 and 0.714, respectively. Optimal HbA1c cutoffs for diagnosing diabetes and prediabetes were 6.0% (sensitivity 83.7%, specificity 87.6%) and 5.7% (sensitivity 60.6%, specificity 72.1%), respectively, although the cutoff for prediabetes showed low accuracy (67.6%) and a high false-negative rate (39.4%). Agreement between HbA1c categorization and OGTT-based diagnosis was low in diabetes (κ = 0.399) and prediabetes (κ = 0.324). In Japanese subjects, the HbA1c cutoff of 6.0% had appropriate sensitivity and specificity for diabetes screening, whereas the cutoff of 5.7% had modest sensitivity and specificity in identifying prediabetes. Thus, HbA1c may be inadequate as a screening tool for prediabetes.

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We confirmed that rs2289360, rs2011616, and rs2304682 in the human EMILIN1 gene, as well as the haplotype constructed using rs2536512, rs2011616, and rs17881426 are useful genetic markers of EH in Japanese men.