Biomedical subjects

Kei Kamide

Publications and source records attributed to Kei Kamide.

At least 37 records · Page 2Linked to original sources

PubMed2004

Identification of gene polymorphism in lipocalin-type prostaglandin D synthase and its association with carotid atherosclerosis in Japanese hypertensive patients.

Recent reports suggested that lipocalin-type prostaglandin D synthase (L-PGDS) is implicated in atherogenesis. In the present study, we investigated the polymorphism of the L-PGDS gene and examined its relationship with the severity of carotid atherosclerosis which is determined as the maximum intima-media thickness in the common carotid artery (C-IMT(max)). We identified 6 single nucleotide polymorphisms (SNPs) of the L-PGDS gene in Japanese. A rare SNP with an amino acid change (1535C>G in exon 4, Leu79Val) and a common SNP (4111 A>C in 3'-untranslated region) were selected for genotyping in 782 Japanese hypertensive subjects. There was no significant difference among genotypes in 1535C>G, however, in 4111 A>C, serum levels of high-density lipoprotein (HDL) cholesterol were significantly higher in subjects with A/A genotype than those with A/C and C/C genotypes. C-IMT(max) was significantly smaller in subjects with A/A genotype than those with A/C and C/C. Logistic regression analysis revealed that the presence of A/A genotype significantly reduced the risk for increased C-IMT(max), even after adjustment for other known risk factors [adjusted odds ratio: 0.71 (95% CI: 0.58-0.88)]. Our results suggested that 4111 A>C polymorphism in the L-PGDS gene contributes to the development of carotid atherosclerosis in Japanese hypertensive patients.

Adult↗

PubMed2004

Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population.

The deletion of thiazide-sensitive Na-Cl cotransporter ( TSC, SLC12A3) causes Gitelman's syndrome characterized by low blood pressure, while deletions of the WNK1 ( PRKWNK1) and WNK4 ( PRKWNK4) genes cause familial hypertension known as pseudohypoaldosteronism type II. Recent studies have revealed that cell surface expression of TSC is regulated by WNK1 and WNK4. We hypothesized that molecular variations in TSC, WNK1, and WNK4 could lead to an increased morbidity of hypertension. We identified 52, 35, and 21 polymorphisms in Japanese hypertensives by sequencing the entire coding regions of TSC, WNK1 and WNK4, respectively. Twenty-one representative polymorphisms were genotyped in 1,818 Japanese individuals (771 subjects with hypertension and 1,047 controls) randomly sampled in Suita city. The results indicated that the systolic blood pressure in men with the CT+TT genotype in WNK4 C14717T was 3.1 mmHg higher than those with the CC genotype ( p=0.042) after adjustment with confounding factors such as age, BMI, hyperlipidemia, diabetes mellitus, antihypertensive drug use, smoking, and drinking. Multivariate logistic regression analysis (with adjustment for the same parameters) in men revealed that the odds ratio for the presence of hypertension of the CT+TT genotype in C14717T to the CC genotype was 1.62 ( p=0.010, 95% confidence interval, 1.12-2.33). Association of TSC and WNK1 with hypertension was not observed. In conclusion, our study suggests the possible involvement of WNK4 in essential hypertension in a Japanese general population.

Adult↗

PubMed2004

A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population.

To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 ( ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(-273)C ( P=0.0074), C(-297)T ( P=0.0195), and IMS-JST071749 ( P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(-273)C genotype was influential in another set of subjects ( P=0.0310, n=743). However, the distribution of the ABCA1 G(-273)C genotype in subjects with MI ( n=598) was not different from that in the control population ( n=801). These results indicate that ABCA1 G(-273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.

ATP Binding Cassette Transporter 1↗

PubMed2004

Three novel missense mutations of WNK4, a kinase mutated in inherited hypertension, in Japanese hypertensives: implication of clinical phenotypes.

BACKGROUND: Mutations in serine-threonine kinase WNK4 with no lysine (K) at a key catalytic residue cause familial hypertension known as pseudohypoaldosteronism type II (PHAII). The objective of this study was to test whether more subtle changes of WNK4 could be implicated in hypertension or renal failure. METHODS: We screened 956 Japanese patients with hypertension or renal failure for mutations in exons 7 and 17 in the WNK4 gene where the mutations were identified in patients with PHAII. RESULTS: We identified three novel missense mutations, Met546Val (n = 2) and Pro556Thr (n = 2) in exon 7, and Pro1173Thr (n = 1) in exon 17, in a heterozygous state in addition to four single nucleotide polymorphisms including one synonymous mutation (Ala547Ala). Results of genotyping Met546Val and Pro556Thr mutations indicated that these mutations were not present in a Japanese general population (n = 1875). CONCLUSIONS: The present study indicated that a systematic screening of WNK4 in a large set of patients with hypertension or renal failure detected some rare genetic variants. Although substantial contribution of three novel missense mutations in exons 7 and 17 of WNK4 to the genetics of hypertension or renal failure is still unclear, these mutations in the WNK4 gene identified in Japanese hypertensives but not in a general population may contribute to hypertension and progression of hypertensive complications to some extent.

Aged↗

PubMed2004

Plasma asymmetric dimethylarginine and coronary and peripheral endothelial dysfunction in hypertensive patients.

BACKGROUND: The attenuation of coronary flow reserve (CFR) and endothelium-mediated vasodilation of the brachial artery (EMV-BA) have been frequently reported in hypertensive patients. The present study investigated the link between CFR and EMV-BA in hypertensive patients. We hypothesized that changes in serum asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and concomitant insulin resistance may be underlying factors connecting the two pathologic alterations. METHODS: A total of 75 patients (30 men and 45 women, 61.5 +/- 10.1 years of age) with essential hypertension and without coronary artery disease and diabetes mellitus were included in the study. Measurements of CFR were made using adenosine-triphosphate stress transthoracic Doppler echocardiography, and forearm EMV-BA was measured by venous occlusion strain gauge plethysmography. A plasma ADMA assay and a 75-g oral glucose tolerance test were also performed. RESULTS: Average CFR and EMV-BA values were 2.54 +/- 0.63 and 86.0 +/- 54.7%, respectively. A significant correlation was found between CFR and EMV-BA (r = 0.493, P <.001). Both CFR and EMV-BA were also significantly correlated with age and plasma ADMA concentration, but were not correlated with insulin resistance, plasma insulin, or left ventricular mass. Multiple regression analysis revealed that ADMA was the only statistically independent parameter associated with CFR and EMV-BA. CONCLUSIONS: The similar deterioration in endothelial function in coronary and peripheral vascular territories may be mainly due to increased plasma ADMA concentration. Plasma ADMA appears to play a major role in endothelial dysfunction in hypertensive patients, independent of insulin resistance or left ventricular hypertrophy.

Aged↗

PubMed2004

Identification of 21 single nucleotide polymorphisms in human hepatocyte growth factor gene and association with blood pressure and carotid atherosclerosis in the Japanese population.

It has been suggested that circulating concentrations of hepatocyte growth factor (HGF) are increased in individuals with vascular endothelial damage, such as in hypertensive patients and subjects with atherosclerosis. Because the influence of genetic variation of HGF has not been examined, we identified single nucleotide polymorphisms (SNPs) in the HGF gene, and investigated the association between these SNPs and blood pressure or carotid atherosclerosis in the Japanese general population. We identified 21 SNPs in the HGF gene by direct sequencing in a test population of 32 Japanese subjects. Among them, considering allele frequency and linkage disequilibrium, three SNPs, C-1652T in the promoter, T43839A in intron 8, and T44222C in intron 9, were genotyped in 2412 members of the Japanese general population randomly selected from the residents in Suita city. None of the three SNPs were significantly associated with blood pressure. After adjusting for age, smoking habits, consumption of alcohol, and the presence of diabetes mellitus and dyslipidemia, female subjects with the T allele of T43839A had more severe carotid atherosclerosis compared to individuals with the A allele. This study provides the first evidence that HGF may be a candidate susceptibility loci that affects the progression of atherosclerosis in Japanese subjects.

Adult↗

PubMed2004

Insulin-mediated regulation of the endothelial renin-angiotensin system and vascular cell growth.

OBJECTIVE: Insulin has a growth-stimulating effect for vascular tissue. At the tissue level, the vascular renin-angiotensin system (RAS) may be involved in the progression of atherosclerosis or vascular hypertrophy. We previously reported that the vascular RAS activity is activated in vascular smooth muscle cells (SMC) by insulin stimulation. However, the effect of insulin on the RAS in endothelial cells (EC) is not fully understood. METHODS: Cultured human EC were incubated with or without insulin. After incubation for 48 h, cellular angiotensinogen and renin mRNA expression and levels in the cells were quantified by slot-blot hybridization and radioimmunoassay. Angiotensin I converting enzyme (ACE) activity in EC homogenates was measured by modified Cushman and Cheung method. EC growth and SMC with or without EC using co-culture were assessed by 3H-thymidine uptake for evaluation of their growth. RESULTS: All doses of insulin (10, 100, 1000 microU/ml) decreased angiotensinogen and renin mRNA expression (angiotensinogen: 19.3%, P < 0.05; 25.4%, P < 0.01; 26.2%, P < 0.01, renin: 12.9%, P < 0.05; 21.3%, P < 0.01; 14.3%, P < 0.05, respectively). Both cellular angiotensinogen and renin level were also reduced by high levels of insulin. Neither 10 nor 100 microU/ml insulin increased cellular angiotensin converting enzyme (ACE) activity (2.17 to 3.48-folds, P = 0.077, 0.125, respectively) significantly, but 1000 microU/ml insulin strongly up-regulated ACE activity by 16.67-folds (P = 0.001) in cultured EC. For the co-culture with EC and SMC, 100 microU/ml insulin was not able to induce SMC but 1000 microU/ml insulin accelerated SMC growth in the co-culture. In contrast insulin that was over 100 microU/ml induced SMC growth in the sole culture of SMC. CONCLUSION: Either low or high levels of insulin suppressed angiotensinogen and renin expression, however, high doses of insulin stimulated ACE activity in cultured human aortic EC. This may indicate that insulin regulates vascular cell growth and endothelial function via bifunctional modification of the vascular angiotensin generation.

Angiotensinogen↗

PubMed2004

Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives.

Liddle's syndrome is an autosomal dominant disease characterized by sodium-sensitive early hypertension and mutations in either the beta- or gamma-subunit of the amiloride-sensitive epithelial sodium channel encoded by SCNN1B and SCNN1G. We sequenced the 381 bp-coding regions in exon 13 of SCNN1B and the 381 bp-coding regions in exon 12 of SCNN1G in 948 and 953 Japanese patients with hypertension, respectively. In the SCNN1B gene, we identified three missense mutations, P592S (n=3), T594M (n=2), and E632K (n=1) in a heterozygous state in addition to four synonymous ones, Ile515 (n=1), Ser520 (n=19), Ser533 (n=1), and Thr594 (n=11). In the SCNN1G gene, we identified three missense mutations, A578V (n=1), P603S (n=1), and L609F (n=1) in a heterozygous state in addition to two synonymous ones, Ile550 (n=1) and Leu649 (n= 91, heterozygous; n=2, homozygous). We did not identify the same mutations previously reported in Liddle's syndrome kindreds. Two of the six hypertensive patients with missense mutation in the SCNN1B gene showed atypical renin and aldosterone levels, though one of them was diagnosed with renovascular hypertension. One patient with T594M in the SCNN1B gene was resistant to hypertension. The roles of these missense mutations in the SCNN1B or SCNN1G gene identified in hypertensive patients are not clear in the pathogenesis of hypertension and the regulation of electrolytes. Thus, further investigation of these mutations, including functional analyses, will be needed.

Aged↗

PubMed2004

Evaluation of the Lys198Asn and -134delA genetic polymorphisms of the endothelin-1 gene.

Endothelin-1 (ET-1) is a potent vasoconstrictor and shows various pharmacological responses. Two single nucleotide polymorphisms in the ET-1 gene (EDN1) have been reported to be associated with blood pressure (BP). One is the Lys198Asn polymorphism, which showed a positive association with BP in overweight people. Another is the 3A/4A polymorphism (-134delA) located in the 5'-untranslated region. In this study, we investigated the expression of the Lys198Asn polymorphism in ET-1 in vitro, as well as the association between either of the two polymorphisms and the plasma ET-1 level. We expressed both the major (Lys-type) and minor type (Asn-type) preproET-1 in three different cell lines, and measured the levels of ET-1 and big ET-1 in the culture supernatant. There was no significant difference in the levels of ET-1 or big ET-1 between the Asn-type and Lys-type transfectant. In the association study, the plasma levels of ET-1 in 54 hypertensive patients having an amino acid substitution from Lys to Asn at position 198 were not different from those of hypertensives without the substitution. However, we found a significant difference in ET-1 levels between individuals with the 3A/3A and 3A/4A genotypes. Our transient expression study indicates that the Lys198Asn polymorphism may not directly affect ET-1 and big ET-1 production. Another variant in the EDN1 gene in linkage disequilibrium with the Lys198Asn polymorphism may be responsible for the association with BP, or the interaction between the EDN1 Lys198Asn polymorphism and other factors such as obesity may be involved in the mechanisms elevating BP in vivo.

5' Untranslated Regions↗

PubMed2004

Association of genetic polymorphisms of sodium-calcium exchanger 1 gene, NCX1, with hypertension in a Japanese general population.

The Na+/Ca2+ exchanger (NCX) is a membrane protein involved in calcium homeostasis, catalyzing the exchange of one Ca2+ ion for three Na+ ions across the cell membrane. The Na+/Ca2+ exchange has been suggested to play a role in the pathogenesis of hypertension. Therefore, we examined whether genetic variations in NCX1 were associated with hypertension. Among 15 polymorphisms identified in 96 hypertensive subjects by sequencing the entire exon and promoter regions of NCX1, 7 representative polymorphisms with a minor allele frequency of greater than 4% were genotyped in 1,865 individuals, of whom 787 were hypertensive and 1,072 were normotensive. These subjects were residents of Suita City and were randomly selected as a population for the Suita cohort study. Multivariate logistic regression analysis performed after adjusting for age, body mass index, hyperlipidemia, diabetes mellitus, smoking, and drinking revealed that the -23200T>C and -23181T>C polymorphisms in the 5' upstream region of exon 1c were significantly associated with hypertension in men (-23200T>C: CC vs. TC+TT: odds ratio=0.61; 95% confidence intervals: 0.39 to 0.97; p =0.04) and in women (-23181T>C: CC vs. TC+TT: odds ratio=1.45; 95% confidence intervals: 1.04 to 2.02; p =0.03), respectively. Thus, our study suggests that NCX1 is one of the genes related to susceptibility to essential hypertension in the Japanese general population.

Aged↗

PubMed2004

The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics.

The response of blood pressure to thiazide diuretics (TZDs) differs among individuals. The prediction of the antihypertensive effect of TZDs is important for realizing individualized therapy in the management of hypertension. The aim of this study was to identify the single nucleotide polymorphisms (SNPs) susceptible to the antihypertensive effect of TZDs, particularly focusing on genes related to water-electrolyte absorption in the kidney. Seventy-six outpatients (mean age, 65.4+/-9.0 years) with essential hypertension (EHT) taking TZDs were retrospectively assessed. We defined as responders (R) those whose mean blood pressure was lowered by more than 5 mmHg after the use of TZDs. Forty-eight SNPs in 17 genes (ADD1, GNB3, TSC [SLC12A3], MLR [NR3C2], NCX1 [SLC8A1], WNK1, WNK4, AGT, ACE, AT1 [AGTR1], CYP11B2, ADRB1, ADRB2, ADRB3, ADRA1A, ADRA1B, ADRA2A) were genotyped in the 76 patients. The SNPs in TSC, MLR, NCX1, WNK1, and WNK4 were identified by direct sequencing and those with minor frequencies of greater than 5% were genotyped in this study. The comparison of polymorphism prevalence between R and non-responders (NR) showed significant differences in TSC C1784T (C allele vs. T allele, odds ratio (OR)=3.81, p =0.016, confidence interval (CI): 1.25-11.63) and ADRB3 T727C (Trp64Arg) (T allele vs. C allele, OR=4.59, p =0.005, CI: 1.54-13.68). The blood pressure (BP) in patients homozygous for the major alleles of both TSC C1784T and ADRB3 T727C were significantly reduced by TZD treatment; however, the BP in those homozygous for the minor allele and heterozygous (TSC C1784T: TT+CT; ADRB3 T727C: CC+CT) for both SNPs were not significantly changed after TZD treatment. Both newly detected TSC C1784T and ADRB3 T727C are gene polymorphisms susceptible to the antihypertensive effect of TZDs in patients with EHT. Thus, the prediction of BP reduction by TZDs may be possible by evaluating these two SNPs.

Benzothiadiazines↗

PubMed2004

[Hypertension].

Hypertension is one of most important components of metabolic syndrome. Main etiology of metabolic syndrome is supposed to be due to insulin resistance. Insulin resistance/hyperinsulinemia induces blood pressure elevation by sodium retention, activation of sympathetic nervous system and renin-angiotensin system(RAS) and promotion of vascular cell growth. Moreover, activated RAS, actually angiotensin II, and salt intake lead insulin resistance by inhibiting insulin signaling. Our laboratory revealed the close relationship between the vascular RAS and the action of insulin on the vasculature. This section reviewed recent understandings about hypertension in metabolic syndrome focusing on its pathophysiologic mechanisms and antihypertensive therapy.

Humans↗

PubMed2004

Diagnostic and prognostic value of plasma brain natriuretic peptide in non-dialysis-dependent CRF.

BACKGROUND: Brain natriuretic peptide (BNP) is useful for the evaluation of ventricular dysfunction in patients with various cardiac diseases. However, its diagnostic value has been considered to be limited in patients with chronic renal failure (CRF) because renal dysfunction itself may affect BNP levels. This study is designed to clarify the diagnostic and prognostic value of plasma BNP level in patients with CRF. METHODS: In 103 non-dialysis-dependent patients with CRF without heart failure and 60 hypertensive patients with normal renal function, echocardiographic examinations and BNP measurements were performed. RESULTS: Plasma BNP level was much greater in patients with CRF than in hypertensive controls; however, multiple regression analysis showed that left ventricular (LV) end-diastolic volume (EDV) index (LVEDVI) and the difference in mitral and pulmonary venous atrial wave duration (Ad-PVad), a marker of LV end-diastolic pressure, were independent determinants of plasma BNP levels in patients with CRF. The influence of LV overload (LVEDVI > or = 75 mL/m 2 and/or Ad-PVad < 0 milliseconds) on plasma BNP levels in subjects with CRF was independent of the severity of renal dysfunction. From Kaplan-Meier event-free curves (mean follow-up, 13 months), the incidence of heart failure was much greater in patients with a plasma BNP level of 150 pg/mL or greater ( P < 0.001). By means of multivariate Cox regression analysis, high plasma BNP level was the strongest predictor for heart failure events (hazard ratio, 6.31; P < 0.001). CONCLUSION: These findings support plasma BNP level as a reliable marker of LV overload, even in nondialysis patients with CRF. Also, a high BNP level (> or =150 pg/mL) may have powerful predictive potential for heart failure in these patients.

Aged↗

PubMed2003

Role of endothelin-1 induced by insulin in the regulation of vascular cell growth.

Insulin is not only a growth factor for vascular cells, but also an inducer of other vasoactive substances such as endothelin-1 (ET-1) in vascular cells. The aim of the present study was to assess the role of endothelial cells (EC) in insulin mediated vascular smooth muscle cell (VSMC) proliferation. Cultured human aortic EC and VSMC were separately incubated. EC were stimulated with insulin (0 to 1000 microU/mL) for 24 h, in the presence or absence of anti-insulin-growth factor-1 (anti-IGF-1) receptor antibody (alphaIR(3)) or a nonselective ET-1 receptor antagonist (TAK044). Cell proliferation was measured by determining (3)H-thymidine uptake. Although 10 microU/mL insulin did not affect ET-1 production in the EC culture medium, a higher concentration of insulin stimulated it. Production of ET-1 in EC was activated by insulin via the IGF-1 receptor, inasmuch as alphaIR(3) blocked insulin mediated upregulation of ET-1. There was no significant difference in (3)H-thymidine incorporation in the presence of insulin (up to 1000 microU/mL) or TAK044. Culture medium from EC stimulated with insulin enhanced VSMC proliferation, which was almost totally suppressed by TAK044. Insulin induced VSMC growth dose dependently when VSMC were cultured alone. In contrast, insulin at concentrations of 100 microU/mL or lower failed to stimulate growth of co-cultured VSMC, but only at 330 microU/mL or higher concentrations stimulated VSMC growth in this system. Of interest, VSMC proliferation was greatest when L-NAME was added and co-cultured with EC. In summary, a severely hyperinsulinemic state may regulate VSMC and EC proliferation via activation of vasoactive substances such as ET-1 and nitric oxide induced by insulin.

Aorta↗

PubMed2003

Efficacy of screening for primary aldosteronism by adrenocortical scintigraphy without discontinuing antihypertensive medication.

BACKGROUND: Recently, it has been proposed that discontinuation of antihypertensive medications is not necessarily essential for the measurement of plasma aldosterone-to-renin ratios. We examined the efficacy of adrenocortical scintigraphy performed without modification of antihypertensive medications. METHODS: A retrospective study was conducted on 119 patients, in whom functional tests, anatomic studies, and adrenocortical scintigraphy were replete. Interrelationship among these was studied. The patients tested were being treated with antihypertensive medications from several classes including angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers, diuretics, and spironolactone. RESULTS: Significantly higher percentage of scintigraphy positive patients had plasma aldosterone-to-renin ratio of greater than 25:1. Positive rate for adrenal nodules by anatomic studies was significantly higher in the scintigraphy positive patients than in the scintigraphy negative patients. Finally, the percentage of patients who underwent adrenalectomy was higher in the scintigraphy positive patients than in the scintigraphy negative patients. CONCLUSIONS: We conclude that adrenocortical scintigraphy is a valid evaluation tool for primary aldosteronism and that the discontinuation of antihypertensive medications is not a requirement for this test.

Adult↗

PubMed2003

Influence of low high-density lipoprotein cholesterol on left ventricular hypertrophy and diastolic function in essential hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy and LV diastolic dysfunction, which are common cardiac changes in hypertensive patients, are modified by several nonhemodynamic (eg, genetic, neurohumoral, and metabolic) factors. However, the influence of serum lipids on these LV changes has not been sufficiently studied. Although low high-density lipoprotein (HDL) cholesterol is well known to be a major risk factor for coronary heart disease, it is unclear whether HDL cholesterol plays a role in hypertensive heart disease. METHODS: In 274 patients with treated essential hypertension, two-dimensional and Doppler echocardiography were performed, and LV mass, ratio of peak velocity of atrial filling to early diastolic filling (A to E ratio [A/E]), and deceleration time of the E-wave were evaluated. The relationship of dyslipidemia, especially low HDL cholesterol, to LV hypertrophy and diastolic function was investigated in these patients. RESULTS: In a univariate regression analysis, HDL cholesterol was inversely associated with LV mass, A/E, and deceleration time. The association of HDL cholesterol with LV diastolic function was observed in both men and women. Its association with LV mass was gender-dependent, being significant only in women. Triglycerides were weakly correlated with LV mass and A/E, but total and low-density lipoprotein cholesterol had no correlations with these indices. In a multiple regression analysis, only low HDL cholesterol among several lipid levels was an independent predictor of both LV mass and LV diastolic dysfunction. CONCLUSIONS: Our findings suggest that low HDL cholesterol may unfavorably modify LV structure and diastolic function in patients with treated essential hypertension.

Aged↗

PubMed2003

An alternative fast and convenient genotyping method for the screening of angiotensin converting enzyme gene polymorphisms.

Insertion/deletion (I/D) polymorphisms in intron 16 of the angiotensin converting enzyme gene (ACE) are associated with the plasma angiotensin converting enzyme (ACE) levels, and individuals with the DD allele have been reported to be more susceptible to cardiovascular disease than those without. The conventional genotyping method for the screening of I/D polymorphisms, which involves polymerase chain reaction (PCR)-gel electrophoresis, is laborious and time-consuming. In this study, we assessed the use of TaqMan-PCR genotyping for the screening of I/D polymorphisms as a replacement for the conventional method. We genotyped seven single nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with the I/D polymorphisms, and calculated the LD coefficients of the I/D polymorphisms. We found that three polymorphisms, rs4331, rs4334 and rs4341, exhibited the highest LD coefficients (D' = 1.000; r2 = 0.967) and that the genotyping of rs4341 by the TaqMan-PCR method yielded the best discrimination among the different genotypes. Genotyping of 511 samples took only 2 h and the amount of DNA required for each test was only 6 ng by the TaqMan-PCR method using rs4341. In the course of this study, we identified a novel additional polymorphism (a deletion of six amino acids) in exon 13, near rs4316. The deletion allele encoded the testicular ACE, but not the plasma ACE. We concluded that genotyping of the rs4341 ACE polymorphism by the TaqMan-PCR method is a fast and convenient alternative method for direct I/D genotyping. We also concluded that testicular ACE may manifest a deletion of six amino acids that may result in deleterious function of this enzyme.

Adult↗

PubMed2003

Carotid intima-media thickness is correlated with impairment of coronary flow reserve in hypertensive patients without coronary artery disease.

Hypertensive individuals occasionally experience angina-like chest pain despite having angiographically normal coronary arteries, and the etiology of this phenomenon has been suggested to be associated with depressed coronary flow reserve (CFR). Carotid intima-media thickness (IMT) assessed by ultrasound is correlated with not only cerebrovascular disease but also coronary artery disease and left ventricular hypertrophy (LVH). The aim of our study was to investigate the association between CFR and carotid IMT in patients with essential hypertension. We performed transthoracic Doppler recording of diastolic coronary flow velocity in the left anterior descending coronary artery at baseline and after maximal vasodilation by adenosine triphosphate infusion in 24 normotensive subjects and 125 hypertensive patients. CFR was defined as the ratio of hyperemic to basal averaged peak coronary flow velocity. Common cardiovascular risk factors, left ventricular mass index (LVMI), relative wall thickness (RWT), and carotid IMT were evaluated. The CFR of hypertensive patients (2.55 +/- 0.52) was significantly decreased compared with that of normotensive subjects (3.15 +/- 0.45). CFR showed a significant correlation with age, systolic blood pressure, RWT, and carotid IMT. Stepwise regression analysis revealed that, among carotid IMT, LVMI and RWT, only carotid IMT was a strong and independent parameter for predicting CFR in hypertensive patients. In conclusion, B-mode ultrasound scanning of the carotid artery seemed to be of clinical value in the screening of patients with LVH and impaired microcoronary circulation. These associations may explain the links between cardiac and cerebrovascular involvements in patients with hypertension.

Aged↗