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Masayoshi Soma

Publications and source records attributed to Masayoshi Soma.

At least 19 recordsLinked to original sources
PubMed2006

Genotyping of triallelic SNPs using TaqMan PCR.

Methods for analysis of single nucleotide polymorphisms (SNP) are well developed. However, most ready-made SNP genotyping kits (e.g., those that use TaqMan PCR) are based on the assumption that the SNP is biallelic. Thus, most kits are unsuitable for triallelic SNPs. We have experienced difficulty genotyping an SNP using TaqMan PCR. In the present study, we developed a method of genotyping a triallelic SNP (rs3091244: alleles C, A and T) using TaqMan PCR. We used 2 different genotyping kits: one for C/A allele genotyping, and one for C/T allele genotyping. The results of these 2 kits were combined to complete the genotyping. The subjects were 320 essentially healthy elderly Japanese. The frequencies of the C, A and T alleles were 0.78, 0.155 and 0.065, respectively. This double-tube method using TaqMan SNP Genotyping Assays was very accurate and convenient, and it should be useful for genotyping in case-control association studies or linkage studies.

Aged↗
PubMed2006

An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension.

Cold-induced autoinflammatory syndrome 1 (CIAS1) gene is a member of the NALP subfamily of the CATERPILLER protein family that is expressed predominantly in peripheral blood leukocytes, which is to regulate apoptosis or inflammation through the activation of NF-kappaB and caspase. Recent genetic analyses suggested an association between inflammation and oxidative stress-related genes in the development of hypertension. This is the first genetic study indicating an association between the CIAS1 gene and susceptibility to essential hypertension (EH). The frequency of subject with the homozygote of 12 repeat allele was significantly higher in patients with hypertension compared with control subjects (987 cases, 924 controls) (P=0.030; odds ratio=1.24) at a novel VNTR polymorphism of CIAS1 intron 4 loci. We also found that the mean of systolic blood pressure of homozygotes of 12 repeat allele was 6.4 mmHg higher than those of homozygotes of non-12 repeat allele in male random population (P=0.009). The frequency of six SNPs spanning of the CIAS1 gene was not significantly between patients and controls. The real-time PCR analysis showed that among healthy young adults, 12-12 subjects expressed CIAS1 mRNA in peripheral leukocytes significantly more abundantly than homozygote of non-12 repeat alleles subjects (P<0.05). Reporter gene assay of the CIAS1-VNTR in HL60 stimulated by lipopolysaccharides showed that the intronic sequence involving 12 repeat increased the expression of luciferase compared with 9, 7, and 6 repeats. Thus, we propose here the CIAS1 is associated with EH through the dominant expression of transcripts, which may depend on the CIAS1-VNTR genotype.

Alleles↗
PubMed2006

Mutation of the follicle-stimulating hormone receptor gene 5'-untranslated region associated with female hypertension.

Inactivating mutations in the follicle-stimulating hormone receptor (FSHR) gene have been reported to cause hereditary hypergonadotropic ovarian failure. It has been found recently that the FSHR knockout mouse exhibits hypertension. The aim of the present study was to investigate the association between polymorphisms in the human FSHR gene and essential hypertension (EH) by using single nucleotide polymorphisms (SNPs). We selected 5 SNPs in the gene (rs1394205, rs2055571, rs11692782, rs1007541, and rs2268361) and performed 2 genetic case-control studies in different populations. A confirmative case-control study was performed using 1035 EH patients and 1058 age-matched controls. Transcriptional activities were measured with a luciferase assay system. The first case-control study found that the A allele of rs1394205 was significantly higher in EH females (P=0.010). In addition, in the confirmative case-control study, there was a significant difference for this SNP between female normotensive subjects (44.5%) and EH patients (50.7%) (P=0.043). Multiple logistic regression analysis in female subjects also revealed a significant association of subjects with the A allele of rs1394205 with EH (P=0.033), with the odds ratio calculated as 1.68 (95% CI: 1.04 to 2.73). Transcriptional activity of the A allele was 56+/-8% (mean+/-SD) of that observed for the G-type allele (P=0.001). Serum estradiol levels were significantly lower in patients with the A/A genotype than in patients without the A/A genotype (P=0.004). The SNP in the 5'-untranslated region of the FSHR gene affects levels of transcriptional activity and is a susceptibility mutation of EH in women.

5' Untranslated Regions↗
PubMed2006

Correction of copper deficiency improves erythropoietin unresponsiveness in hemodialysis patients with anemia.

We have encountered five hemodialysis patients who had received enteral nutrition and recovered from erythropoietin-resistant anemia with neutropenia after the correction of copper deficiency. We reduced the required doses of recombinant human erythropoietin (rHuEPO) to maintain the target hematocrit levels and three patients were finally weaned from the rHuEPO therapy. Thus, copper deficiency is involved in erythropoietin-resistant anemia in hemodialysis patients.

Anemia↗
PubMed2006

Association study between C-reactive protein genes and ischemic stroke in Japanese subjects.

BACKGROUND: C-reactive protein (CRP) is reported to be involved in the development of atherosclerosis. Elevated CRP levels are considered to be a predictor of ischemic stroke (IS) in elderly individuals. Some single-nucleotide polymorphisms (SNP) are reportedly associated with elevated CRP levels. The aims of this study were to genotype some of the SNP in the human CRP gene and to assess the association between the CRP gene and IS. METHODS: Japanese patients with IS (72.4 +/- 8.2 years of age, n = 152) and elderly Japanese subjects without IS (78.0 +/- 4.2 years of age, n = 304) were genotyped for four SNP of the human CRP gene: rs1341665, rs1800947, rs1130864, and rs1205. Each genotyping was performed using the TaqMan SNP genotyping assay. The haplotype-based association study was assessed with a permutation test. RESULTS: The genotype rs1800947 was statistically significant between patients with IS and control subjects (CC+GC versus GG variant, P = .016 by multiple logistic regression analysis). This analysis revealed that the CC+GC variant of rs1800947 was an independent risk factor of IS. All four SNP were located in one haplotype block. The haplotype was constructed using rs1341665, rs1800947, and rs1130864, in that order. There was a significant association between IS and the C-C-C haplotype (P = .015). CONCLUSIONS: The rs1800947 SNP and the C-C-C haplotype in the CRP gene appear to be prognostic markers of ischemic stroke and this polymorphism could be a useful genetic marker.

Aged↗
PubMed2006

The influence of uremic serum on interleukin-1beta and interleukin-1 receptor antagonist production by peripheral blood mononuclear cells.

We investigated whether or not uremic serum has an influence on IL-1beta and IL-1Ra production by normal peripheral blood mononuclear cells (PBMC). Four groups of subjects were divided into healthy controls and non-dialyzed patients with chronic renal failure (CRF), patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients. We examined cytokine concentrations and cytokine production by PBMC from a normal subject at the density of 2.5 x 10(6) cells/mL incubated with 25% serum in the medium and serum containing polymyxin-B or lipopolysaccharides (LPS). IL-1Ra concentrations in the serum of the uremic groups were significantly higher than those of the controls. In IL-1beta production by PBMC in medium with both serum and serum containing polymyxin-B, these values in the uremic groups were significantly higher than in the controls. In IL-1Ra production with serum containing polymyxin-B, these values in the uremic groups were significantly higher than in the controls. In contrast, in IL-1Ra production by PBMC in medium with serum containing LPS, these values in the uremic groups were significantly lower than in the controls. It was concluded that uremic serum not only contains nonendotoxemic cytokine-inducing substances, but also shows impaired cytokine production by PBMC in response to LPS.

Adult↗
PubMed2006

Haplotypes of the plasminogen activator gene associated with ischemic stroke.

Ischemic stroke (IS) is thought to be a multifactorial disorder associated with genetic backgrounds and environmental factors. In the circulating plasma, tissue plasminogen activator (tPA) catalyzes the reaction from plasminogen to plasmin. If there is a functional disability of tPA, induction of thrombosis and infarction disorders can occur. The aim of this study was to perform a haplotype-based case-control study using single nucleotide polymorphisms (SNPs) in the human tPA gene, and to assess the association between the tPA gene and IS. We genotyped 182 IS individuals and 403 controls for five SNPs in the human tPA gene, rs7007329, rs732612, rs8178750, rs2020922, and rs4471024. Using these five SNPs, a haplotype-based case control study was performed. There were seven SNP combinations that exhibited significant differences in the overall distribution between the IS and control groups. Linkage disequilibrium analysis showed that the combination of rs7007329 and rs8178750 was useful in identification of the susceptibility haplotype. The frequency of the G-T haplotype at rs7007329-rs8178750 was significantly higher in the IS group (1.2%) as compared to the control group (0.0%) (p = 0.003). Diplotype analysis also showed a significant association of the diplotype with the G-T haplotype at rs7007329-rs8178750 (OR:11.4, 95%CI:1.32-97.9, p = 0.013). These results suggest that the G-T haplotype at rs7007329-rs8178750 of the tPA gene is a genetic marker for IS, and that tPA or a neighboring gene is a susceptibility gene for IS.

Aged↗
PubMed2006

Polymorphism of the C-reactive protein (CRP) gene is related to serum CRP Level and arterial pulse wave velocity in healthy elderly Japanese.

The objective of this study was to clarify relationships between the C-reactive protein (CRP) gene and both the serum level of CRP and arterial pulse wave velocity (PWV), using haplotype analysis of healthy elderly Japanese. Five single-nucleotide polymorphisms (SNPs) of the human CRP gene (rs1341665, rs3091244, rs1800947, rs1130864 and rs1205) were used to genotype 315 healthy elderly Japanese subjects (mean age, 77.9 +/- 4.1 years; male/female ratio, 0.96). Linkage disequilibrium was analyzed for the five SNPs. The frequency of each haplotype and diplotype was estimated using the expectation/maximization (EM) algorithm. There were statistically significant associations between the CRP level and two CRP genotypes; the p value for the T allele of rs3091244 (CT + AT + TT vs. CC + CA + AA) was 0.002 (95% confidential interval [CI], 2.1-24), and the p value for the T allele of rs1130864 (TT + TC vs. CC) was 0.002 (95% CI, 2.1-24). The only genotype that was significantly associated with arterial PWV was the C allele of rs1800947, with a p value of 0.039. The haplotype was constructed using rs1341665, rs3091244 and rs1800947, in that order. There was a significant association between the CRP level and the T-T-G haplotype, with a p value of 0.002 (95% CI, 2.1-24). There was a significant association between arterial PWV and the C-C-C haplotype, with a p value of 0.039. We concluded that rs3091244, rs1130864 and the T-T-G haplotype are genetic markers for elevated basal CRP levels. rs1800947 and the C-C-C haplotype appear to be susceptibility markers for atherosclerosis, but this requires confirmation.

Age Factors↗
PubMed2006

A case of adrenocorticotropin-independent bilateral adrenal macronodular hyperplasia (AIMAH) with primary hyperparathyroidism (PHPT).

We report a rare case of ACTH-independent macronodular adrenal hyperplasia (AIMAH) with primary hyperparathyroidism (PHPT). A 57-year-old woman was admitted to our hospital for further examination of secondary hypertension and bilateral adrenal macrotumors. Midnight serum cortisol elevation with undetectable plasma ACTH, increased 24-hour urinary free cortisol excretion, and loss of the normal circadian rhythm in cortisol secretion established the diagnosis of Cushing's syndrome. Total resection of the enlarged left adrenal gland was performed with subsequent steroid replacement. Her general condition improved but serum calcium level increased 3 weeks after surgery. PHPT was diagnosed on the basis of endocrinological examination, although imaging studies failed to detect parathyroid lesion. In summary, we believe this to be the first report of a case of AIMAH with PHPT.

Adrenal Gland Diseases↗
PubMed2005

Genotype and haplotype association study of the STRK1 region on 5q12 among Japanese: a case-control study.

BACKGROUND AND PURPOSE: Cerebral infarction is thought to be a multifactorial disease that is affected by several environmental factors and genetic variants. Gretarsdottir et al identified a candidate locus (STRK1) for cerebral infarction with a significant logarithm of odds score at 5q12 in whites in 2002 and subsequently identified the PDE4D gene as a susceptibility gene at this locus in 2003. The aims of this haplotype-based case-control study were to confirm, using microsatellite markers and single-nucleotide polymorphisms (SNPs), whether PDE4D is also a susceptibility gene for cerebral infarction in Japanese subjects. METHODS: Cerebral infarction was defined as noncardiogenic ischemic stroke with signs and symptoms lasting >1 month in duration. We genotyped 208 Japanese cerebral infarction patients and 270 non-cerebral infarction controls for 31 SNPs, 3 dinucleotide microsatellites, and 1 tetranucleotide variable number of tandem repeat. Haplotypes were constructed and their frequencies compared between the cerebral infarction patients and the controls. RESULTS: The haplotype-based case-control study revealed that in addition to the region of the PDE4D gene (P=0.002), another region (P<0.001) also existed within the STRK1 locus. CONCLUSIONS: The region of the PDE4D gene and the other newly detected region within the STRK1 locus were associated with cerebral infarction.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Erectile dysfunction and its influence on quality of life in patients with essential hypertension.

Epidemiological studies indicated that erectile dysfunction (ED) is more frequent and their quality of life (QOL) is deteriorated in patients with essential hypertension as compared with normotensive subjects. Since both ED and hypertension influence QOL, it is not clear which malady has a more serious influence on QOL. We conducted a case control study to investigate incidence and impact of ED on QOL. In 102 patients aged 40 to 59 under treatment for hypertension (Hypertensive group) and in 245 age-matched normal subjects (Control group), QOL and ED were assessed by SF-36 and IIEF5. Criteria for presence of ED is IIEF5 score less than 12. Age adjusted incidence of ED in Hypertension group was higher than that in Control Group (odds ratio 1.7, P < .05). Multivariate logistic regression analysis showed hypertension was related only to a low score in general health, ED was related to low scores in physical, mental health, emotional, vitality, and general health. These data suggest that the influence of ED on QOL is more serious than hypertension in middle age men.

Adult↗
PubMed2005

Association study of calcitonin-receptor-like receptor gene in essential hypertension.

BACKGROUND: Plasma adrenomedullin (ADM) concentrations increase in patients with hypertension, renal failure, heart failure, essential pulmonary hypertension, myocardial infarction, endotoxin shock, and many other conditions. The ADM receptor is a complex molecule that consists of calcitonin-receptor-like receptor (CRLR) and receptor activity-modifying protein 2 (RAMP2). Because CRLR determines the binding specificity of ADM, the CRLR gene is thought to be a susceptibility gene of hypertension. However, studies have not yet defined the relationship between the CRLR gene and hypertension. The aim of the present study was to investigate relationships between single-nucleotide polymorphisms (SNP) in the human CRLR gene and essential hypertension (EH) in a Japanese population. METHODS: We selected four SNP in the human CRLR gene (rs3771073, rs696574, rs698590, and rs1528233), and we performed a genetic association study in 209 EH patients and 216 age-matched normotensive (NT) individuals. RESULTS: There was no significant difference in overall distribution of genotypes or alleles of any of the SNP between the EH and NT groups. However, among women, the T allele of the SNP rs696574 (C --> T, in intron 6) was significantly more frequent in EH subjects than in NT subjects (P = .032). CONCLUSION: Our findings suggest that rs696574 can be used as a genetic marker of EH in women.

Adult↗
PubMed2005

Haplotype-based case-control study revealing an association between the adrenomedullin gene and proteinuria in subjects with essential hypertension.

Adrenomedullin (AM) has various physiological actions on the cardiovascular system, including vasodilatation, diuresis, natriuresis, inhibition of aldosterone secretion, and increases of the cardiac output, all of which cause hypotension. Since AM plays a role in the pathophysiology of vascular diseases, genes controlling AM might be involved in the development and etiology of essential hypertension (EH). However, there have been few studies examining the relationship between the AM gene and hypertension. The aims of this study were to genotype some of the genetic markers for the human AM gene in Japanese subjects, and via a haplotype-based case-control study, assess the association between and the AM gene and EH or its risk factors, such as hyperlipidemia, renal damage, and proteinuria. We genotyped 205 EH patients and 210 age-matched normotensive (NT) individuals for two single nucleotide polymorphisms of rs4399321, rs7944706 and a microsatellite polymorphism located approximately 5,400 base pairs downstream of the 3' end of the human AM gene. The overall distribution in each variant and haplotype did not significantly differ between the two groups. However, after dividing the groups into those subjects with and without proteinuria, the haplotype analysis revealed a positive association. In conclusion, a possible mutation linked to the haplotype may indicate a genetic predisposition for proteinuria in EH.

Adrenomedullin↗
PubMed2004

An association study in essential hypertension using functional polymorphisms in lymphotoxin-alpha gene.

BACKGROUND: Lymphotoxin-alpha (LTA), a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The substance LTA mediates a wide variety of inflammatory, immunostimulatory, and antiviral responses. In 2002, LTA was identified as a major risk factor for myocardial infarction (MI) in Japanese individuals, in a large-scale case-control study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers in the whole human genome. Essential hypertension (EH) is thought to be a multifactorial disorder involved in endothelial dysfunction and atherosclerosis. Although hypertension is one of the greatest risk factors for MI, there have been no reports estimating the association between EH and LTA. The aim of the present study was to evaluate the association between EH and the LTA gene. METHODS: In the present study, we assessed the association between EH and SNP and haplotypes of the LTA gene in a case-control study of 202 EH patients and 217 age-matched normotensive control subjects. RESULTS: The overall distribution of genotypes for each SNP did not significantly differ between the two groups. Furthermore, the haplotype analysis revealed no association between the EH and normotensive groups. CONCLUSIONS: Polymorphisms of the LTA gene were not associated with EH. This finding suggests differences in genetic backgrounds between EH and MI.

Case-Control Studies↗
PubMed2004

Two medium-chain acyl-coenzyme A synthetase genes, SAH and MACS1, are associated with plasma high-density lipoprotein cholesterol levels, but they are not associated with essential hypertension.

BACKGROUND AND OBJECTIVES: SAH has been proposed as a candidate gene for essential hypertension (EH) because elevated expression of SAH was observed in the kidneys of spontaneously hypertensive rats. Recently, a homology search of SAH in the human genome revealed the presence of the SAH gene family, which includes SAH, MACS1, MACS2, and MACS3. SAH and MACS1 are located within a 150-kb region on human chromosome 16p13.11. SAH and MACS1 are thought to function as acyl-coenzyme A synthetases, which are involved in fatty acid metabolism. In the present study, we analyzed six single nucleotide polymorphisms (SNPs) in the SAH and MACS1 genes in a Japanese population, and examined whether these SNPs contribute to EH and multiple risk factors. METHODS AND RESULTS: We performed association studies of six SNPs in 287 EH patients and 259 normotensive subjects. Multiple logistic linear regression analysis revealed that the allele frequencies of these six SNPs in SAH and MACS1 genes were not significantly different between EH patients and normotensives. SNP in exon 8 of the A/G polymorphism of the MACS1 gene and the G/T SNP in intron 3 of the SAH gene were associated with plasma levels of plasma high-density lipoprotein cholesterol. CONCLUSIONS: SNPs in the MACS1 and SAH genes contribute to plasma levels of high-density lipoprotein cholesterol.

Adenine↗
PubMed2004

A comparison of bicarbonate hemodialysis, hemodiafiltration, and acetate-free biofiltration on cytokine production.

Acetate-free biofiltration (AFB) is a special hemodiafiltration (HDF) modality performed with a base-free dialysate and simultaneous injection of non-pyrogenic sodium bicarbonate solution. The purpose of this study was to investigate the difference of cytokine production by conventional bicarbonate hemodialysis (BCD), standard HDF and AFB in the same patients. Eight stable hemodialysis patients were treated in random order with BCD, HDF and AFB every 4 weeks. The production of interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonist (IL-1Ra) by peripheral blood mononuclear cells (PBMC) was investigated without stimulation and with stimulation by a small amount of endotoxin (ET)-contaminated beta 2-microglobulin (beta 2M) and lipopolysaccharide (LPS) before and after dialysis treatment in the last sessions during all periods. To serve as controls, 14 healthy volunteers participated in this study. In spontaneous IL-1Ra production, the values of before and after AFB were not significantly different from that of the controls, and the values of before and after BCD and before HDF were significantly higher than that of the controls. In LPS-stimulated PBMC, IL-1 beta production before and after AFB was not significantly different from that of the controls, and before and after BCD and HDF was significantly higher than that of the controls. In ET-contaminated beta 2M-stimulated PBMC, IL-1 beta production before and after AFB was not significantly different compared to the controls, and the production was significantly lower than that before and after BCD and HDF. In addition, IL-1Ra production after AFB was not significantly different from the controls, and the production was significantly lower than that before and after BCD and HDF. It was concluded that a lower cytokine production by AFB may have the effect of preventing dialysis-related complications.

Adult↗
PubMed2004

Variable number of tandem repeat of the 5'-flanking region of type-C human natriuretic peptide receptor gene influences blood pressure levels in obesity-associated hypertension.

The gene for natriuretic peptides receptor C (NPRC), which is a candidate susceptibility gene for essential hypertension (EH) or obese hypertension, plays a key role in the regulation of plasma levels and biological effects of natriuretic peptides. The aims of the present study were to find new genetic markers in the 5'-flanking region of the NPRC gene and to assess relationships between variants and phenotypes of EH, including EH in obese patients. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we discovered a novel six-nucleotide repeat polymorphism located 4 base pairs (bp) upstream of the major transcriptional initiation site. We performed association analysis of this variable number of tandem repeat (VNTR) in 242 EH patients and 212 normotensive controls (NT). Although no significant difference in overall frequency of VNTR was found between NT and EH groups, the blood pressure level of EH patients with the 5/6 genotype was significantly higher in obese subjects. This suggests that the VNTR of the 5'-flanking region of the NPRC gene influences blood pressure levels in obesity-associated hypertension.

5' Flanking Region↗