Non-dipping blood pressure variations in adult Kazakhs are derived from decreased daytime physical activity and increased nighttime sympathetic activity.

Many of the elderly Kazakhs have been found to exhibit non-dipping blood pressure variations (BPV). Such variations are seen in both normotensive and hypertensive Kazakhs. The purpose of this study was (1) to determine whether middle-aged Kazakhs also include large numbers of non-dippers, (2) to compare the characteristics of non-dipping and dipping, and (3) to clarify the mechanisms responsible for non-dipping type BPV by examining the autonomic nervous activity and physical activity. We performed ambulatory blood pressure (BP) monitoring. The subjects were divided into two groups (dipping and non-dipping type). We monitored the subjects' physical activity with accelerometry and assessed their autonomic nerve activity by performing a frequency domain analysis of their heart rate variability (HRV). The power spectral density (PSD) of the HRV was calculated using fast Fourier transformation. We analyzed the systolic blood pressure (SBP) variations with the maximum entropy method (MEM). The dippers and non-dippers accounted for 48% and 52% of the subjects, respectively. MEM analysis revealed that the SBP variations of the non-dippers exhibited a 24 hour periodicity with a very weak PSD as well as an ultradian periodicity. The non-dippers exhibited higher low-frequency/high-frequency (LF/HF) ratio and lower HF/(LF + HF) ratios than the dippers, particularly during the nighttime. In addition, the non-dippers performed less physical activity than the dippers. These differences in cardiac autonomic function and physical activity might contribute to the generation of a weak circadian rhythm in SBP, and thus, ultimately lead to the non-dipping SBP variations observed in non-dipper Kazakhs.

Relationship between status of plasma atrial natriuretic peptide and heart rate variability in human subjects.

A relationship may exist between plasma atrial natriuretic peptide (P-ANP) and heart rate variability (HRV), which reflects the activity of the autonomic nervous system. We performed a survey in human subjects to examine the relationship between P-ANP and HRV parameters. Three ethnic groups (Han, Uygur, and Kazakh) provided blood and urine samples and underwent 24-h ambulatory blood pressure monitoring and 24-h ECG recording (24-h Holter ECG). There was a positive correlation between P-ANP and HF, as well as a negative correlation between P-ANP and the LF/HF ratio, in all subjects from the 3 ethnic groups. There was no association of BP with any of the blood, urinary, and HRV parameters. Our results suggested the possibility of a relationship between P-ANP and HRV, which reflects autonomic activity. These findings are consistent with the previous report of a close relationship between ANP and cardiac parasympathetic and/or sympathetic activity.

Association of the smoothelin (SMTN) gene with cerebral infarction in men: a haplotype-based case-control study.

Smoothelin is a specific type of cytoskeletal protein found in smooth muscle cells (SMCs). Several previous research studies have examined the relationship between smoothelin and atherosclerotic plaque. The aim of the present study was to further assess the association between the human SMTN gene and cerebral infarction (CI) using a haplotype-based case-control study. A total of 168 CI patients and 259 supercontrols were genotyped for the five single-nucleotide polymorphisms (SNPs) used as genetic markers for the human SMTN gene (rs2074738, rs5997872, rs56095120, rs9621187 and rs10304). Data were analyzed for three separate groups that included total subjects, men and women. The genotypic distribution of rs10304 for men showed a significant difference between the control and CI groups. In addition, the frequency of the C-T-T-A haplotype (established by rs5997872, rs56095120, rs9621187 and rs10304) was significantly higher in the CI versus the control group (p = 0.013), while the frequency of the C-A-T-G haplotype (established by rs5997872, rs56095120, rs9621187 and rs10304) in the CI group was significantly lower than that seen in the controls (p = 0.021). In conclusion, we confirmed that the haplotype constructed using rs5997872, rs56095120, rs9621187 and rs10304 was a useful genetic marker of CI in Japanese men.

Haplotype-based case-control study of CYP4A11 gene and myocardial infarction.

CYP4A11, which is a member of the cytochrome P450 family, acts mainly as an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite involved in the maintenance of cardiovascular health. Recently, it was reported that many subfamilies of CYP genes have an association with myocardial infarction (MI). The aim of the present study was to assess the association between the human CYP4A11 gene and MI, using a haplotype-based case-control study with a separate analysis of the gender groups. A total of 239 MI patients and 285 controls were genotyped for 3 single-nucleotide polymorphisms (SNPs) of the human CYP4A11 gene (rs2269231, rs1126742, rs9333025). The data obtained via haplotype-based case-control studies were assessed for 3 separate groups: total subjects, men, and women. For the total, men and women groups, the distribution of the genotypes and alleles of the 3 SNPs did not show any significant difference between the MI patients and the control subjects. For the total and the men groups, the overall distribution of the haplotypes constructed with the 3 SNPs significantly differed between the MI patients and control subjects (P < 0.001). Also, for the total and for the men, the frequency of the T-T-A haplotype constructed with the 3 SNPs was significantly lower for the MI patients than for the control subjects (both P < 0.001). The T-T-A haplotype constructed with the 3 SNPs appears to be a protective genetic marker for MI in Japanese men.

Haplotype of smoothelin gene associated with essential hypertension.

Smoothelin is a specific cytoskeletal protein that is associated with smooth muscle cells. The human SMTN gene encodes smoothelin-A and smoothelin-B, and studies using SMTN gene knockout mice have demonstrated that these animals develop hypertension. The aim of the present study was to investigate the association between the human SMTN gene and essential hypertension (EH) using a haplotype-based case-control study. This is the first study to assess the association between essential hypertension and this gene. A total of 255 EH patients and 225 controls were genotyped for the five single-nucleotide polymorphisms (rs2074738, rs5997872, rs56095120, rs9621187 and rs10304) used as genetic markers for the human SMTN gene. Data were analyzed for three separate groups: total subjects, men and women. Although there were no differences for genotype distributions, or the dominant and recessive model distributions noted for total subjects, men and women for all of the SNPs selected for the present study, for the total subjects group, the frequency of the G-C-A-C haplotype constructed with rs2074738-rs5997872-rs56095120-rs9621187 was significantly lower in the essential hypertension patients than in the controls (P = 0.002). The G-C-A-C haplotype appears to be a useful protective marker of essential hypertension in Japanese, and the SMTN gene might also be a genetic marker for essential hypertension.

Automated versus manual measurement of the QT interval and corrected QT interval.

BACKGROUND: The International Conference on Harmonization E14 Guideline specifies detailed assessment of QT interval or corrected QT interval prolongation when developing new drugs. We recently devised new software to precisely measure the QT interval. METHODS AND RESULTS: The QT intervals of all leads for a selected single heart beat were compared between automated measurement with the new software from Fukuda Denshi and manual measurement. With both automated and manual measurement, QT intervals obtained by the tangent method were shorter than those obtained by the differential threshold method, but the extent of correction was smaller. QT interval data obtained by the differential threshold method were more similar to values obtained by visual measurement than were data obtained by the tangent method, but the extent of correction was larger. Variability was related to the T-wave amplitude and to setting the baseline and tangent in the tangent method, while skeletal muscle potential noise affected the differential threshold method. Drift, low-amplitude recordings, and T-wave morphology were problems for both methods. Among the 12 leads, corrections were less frequent for leads II and V(3) -V(6) . CONCLUSION: We conclude that, for a thorough assessment of the QT/QTc interval, the tangent method or the differential threshold method appears to be suitable because of smaller interreader differences and better reproducibility. Correction of data should be done by readers who are experienced in measuring the QT interval. It is also important for electrocardiograms to have little noise and for a suitable heart rate and appropriate leads to be selected.

Correlation of left ventricular pressure changes and left atrial function on strain rate imaging during acute left ventricular ischemia.

The objective of the present study was to evaluate whether left ventricular (LV) pressure changes influence left atrial (LA) function during acute LV ischemia by strain rate imaging. In 11 healthy dogs, the left anterior descending coronary artery was occluded to cause regional acute ischemia. The peak strain rate (PSR) values of the LA walls during the reservoir, conduit, and contractile phases of the LA cycle, as well as the LV pressures, were measured before and after ischemia. All PSR values increased significantly after ischemia (P < 0.001). Left ventricular end-diastolic pressure (LVEDP) increased after ischemia (P < 0.0001) and its percent change was positively correlated with the LA contractile phase and conduit phase percent changes of PSR for the anterior and lateral walls of the atrium (r = 0.72, 0.72, 0.83, and 0.73; P = 0.05, 0.05, 0.002, and 0.01, respectively). LA function is influenced by the change of LVEDP during regional LV ischemia. There is a compensatory increase in wall motion after regional acute LV ischemia.

A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese men.

This study assessed associations between the CYP4F2 gene and myocardial infarction (MI), using a haplotype-based case-control study of 234 MI patients and 248 controls genotyped for 5 single-nucleotide polymorphisms (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For men, G allele frequency of rs2108622 and frequency of the T-C-G haplotype were significantly higher, and frequency of the T-C-A haplotype was significantly lower for MI patients than for controls (P=0.006, P=0.001 and P=0.002, respectively).

Association of the purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene with myocardial infarction in Japanese men.

BACKGROUND: Atherosclerosis leads to myocardial infarction (MI) and P2RY2 plays an important role in this process. The aim of the present study was to investigate the association between human P2RY2 and MI via a haplotype-based case-control study that additionally analyzed the group by sex. METHODS AND RESULTS: The 310 MI patients and 254 controls were genotyped for 5 single-nucleotide polymorphisms (SNPs) of the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936, rs10898909). Data were separately analyzed for the total, male, and female subjects. For men, the GA+AA genotype of rs10898909 was significantly higher in MI patients as compared with controls (P=0.040). Logistic regression analysis found a significant difference for the genotype (P=0.016). As compared with controls, the frequencies of the C-A and T-C-A haplotypes were significantly higher (P=0.016, and P=0.045, respectively) in men, whereas the frequencies of the C-G and T-A-A haplotypes were significantly lower (P=0.023, and P=0.025, respectively) in MI patients. CONCLUSIONS: The GA+AA genotype, as well as the C-A and T-C-A haplotypes, of human P2RY2 could be genetic markers for MI in Japanese men.

A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men.

OBJECTIVE: CYP4A11, a member of the cytochrome P450 family, acts mainly as an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a metabolite involved in blood pressure regulation in humans. Disruption of the murine cyp4a14 and cyp4a10 genes, homologues of human CYP4A11, was reported recently to cause hypertension. The gene-disrupted male mice had higher blood pressure than the gene-disrupted female mice. The present study aimed to assess the association between the human CYP4A11 gene and essential hypertension, using a haplotype-based case-control study including separate analysis of the gender groups. METHODS: The 304 essential hypertension patients and 207 age-matched control individuals were genotyped for three single-nucleotide polymorphisms of the human CYP4A11 gene (rs2269231, rs1126742, rs9333025). Data were assessed for three separate groups: total participants, men and women. RESULTS: For total participants, the genotypic distribution of rs1126742 differed significantly between the two groups (P = 0.005). For total participants, men and women, the recessive model (CC versus TC + TT) of rs1126742 differed significantly between the two groups (P = 0.007, P = 0.043, and P = 0.045, respectively). Logistic regression analysis showed the TC + TT genotype was significantly higher in essential hypertension patients than in control individuals for total participants and men (P = 0.022 and P = 0.043, respectively). The A-T-G haplotype frequency (established by rs2269231, rs1126742, rs9333025) was significantly higher in essential hypertension men than in control men (P = 0.043). CONCLUSIONS: Essential hypertension is associated with the TC + TT genotype of rs1126742 in the human CYP4A11 gene. The A-T-G haplotype appears a useful genetic marker of essential hypertension in Japanese men.

Haplotype-based case-control study of the human CYP4F2 gene and essential hypertension in Japanese subjects.

CYP4F2 acts primarily as an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite involved in the regulation of blood pressure in humans. The aim of the present study was to assess the association between the human CYP4F2 gene and essential hypertension (EH) using a haplotype-based case-control study that included separate analysis of the two gender groups. The 249 EH patients and 238 age-matched controls were genotyped for 5 single-nucleotide polymorphisms (SNPs) of the human CYP4F2 gene (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). Data were analyzed for 3 separate groups: all subjects, and men and women separately. For the total population and for male subjects, the distribution of the dominant model of rs1558139 (CC vs. CT+TT) differed significantly between the EH patients and control subjects (p=0.037 and p=0.005, respectively), with a higher percentage of EH patients showing the CC genotype. Logistic regression showed that, for men, the CC genotype of rs1558139 was more prevalent in the EH patients than in the control subjects (p=0.026), while, for the total population, the difference disappeared (p=0.247). For men, the overall distribution of the haplotypes was significantly different between the EH patients and the control subjects (p=0.042), and the frequency of the T-T-G haplotype was also significantly lower for EH patients than for control subjects (p=0.009). In conclusion, the present results indicate that rs1558139 might be a genetic marker for EH and the T-T-G haplotype might be a protective genetic marker for EH in Japanese men.

Effect of age at menopause on blood pressure in postmenopausal women.

BACKGROUND: A major mechanism of hypertension in many postmenopausal women is deficiency of female gonadal steroids. A long postmenopausal period may thus represent one factor that influences the prevalence of hypertension because of long periods of estrogen loss. METHODS: When we conducted a medical survey in northwestern China, we also asked 150 postmenopausal female subjects to provide age at menopause in a questionnaire. Age at menopause ranged from 37 to 57 years for all subjects. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) in all subjects were obtained from 24-h ambulatory blood-pressure monitoring. RESULTS: An inverse correlation was identified between age at menopause and SBP and DBP, and a positive correlation was found between postmenopausal period and either SBP or DBP. Blood pressure, age at menopause, and postmenopausal period were not significantly related to body mass index, plasma renin activity, glomerular filtration rate, or urinary excretion values of sodium and potassium. CONCLUSIONS: Our results clearly demonstrated that higher blood-pressure levels in postmenopausal women depend on age at menopause and postmenopausal period, but not subjects' age, suggesting that a longer absence of female gonadal steroids represents a major factor contributing to increased blood pressure in elderly women.

Common single nucleotide polymorphisms in Japanese patients with essential hypertension: aldehyde dehydrogenase 2 gene as a risk factor independent of alcohol consumption.

Essential hypertension (EH) is a multifactorial disorder determined by the interaction of environmental and genetic factors. EH patients' responses to these factors may vary, depending on differences in their genes that determine the physiological systems that mediate the response. The purpose of this investigation was to clarify the contributions of genetic background and lifestyle to EH through an association study using some common single nucleotide polymorphisms (SNPs) that should have functional effects on EH phenotypes. We studied the associations between common SNPs of some causal genes related to EH and lifestyle in a Japanese population. The variants of the causal genes were selected based on their functions, including: obesity (adrenergic, beta-3-, receptor: ADRB3), alcohol consumption (aldehyde dehydrogenase 2: ALDH2), water-electrolyte metabolism (guanine nucleotide binding protein [G protein], beta polypeptide 3: GNB3), glycometabolism (peroxisome proliferator-activated receptor gamma: PPARG), lipometabolism (cholesteryl ester transfer protein, plasma: CETP), atherosclerosis (5,10-methylenetetrahydrofolate reductase [NADPH]: MTHFR), and cellular behavior (gap junction protein, alpha 4, 37 kD: GJA4). Case-control association analysis showed a significant association between EH and both the ALDH2 (Lys487Glu) and GNB3 (C825T) variants. Logistic regression analysis indicated that body mass index (BMI) is an important risk factor for EH, and that the GG (Glu/Glu) genotype of ALDH2 was an independent risk factor for EH overall and especially for EH in males. There was no interaction between the ALDH2 genotype and alcohol consumption overall or in male subjects. Our results suggest that the ALDH2 genotype is associated with EH independently of alcohol consumption.

[Transmission and non-transmission portable ECG in home care medicine].

Portable electrocardiography is advantageous in that patients can record ECG by themselves at any time and place. Portable ECG can be classified into two kinds of devices, transmission type and non-transmission type. By using transmission-type portable ECG, patients can obtain an ECG diagnosis from the center by transmitting the recorded ECG. Transmission-type portable ECG is extremely useful for patients needing emergency treatment for such as an attack of ischemic heart disease or arrhythmic event. On the other hand, a patient has to go to a specialist to obtain an ECG diagnosis with the non-transmission-type portable ECG device after recording the ECG alone. As this model is slightly cheaper, and is easy to use, the non-transmission-type portable ECG is good in non-emergency use for early diagnosis and prevention of cardiac disease. Portable ECG is useful for ECG monitoring over time without seeing the patient, not only for symptomatic analysis of the patient. For example, silent myocardial ischemia and arrhythmic events developing during exercise will become clear in periodical portable ECG recording. In particularly, portable ECG is useful for noncontinual ECG monitoring of patients with Brugada syndrome and those administered with antiarrhythmic drugs. Portable ECG increases the opportunity to discover cardiac disease from the aspect of preventive medicine. When patients use a portable ECG during exercise, they can understand whether the exercise is suitable for their heart. Portable ECG is a useful measurement in preventive medicine as described above, not only for the home care of patients.

[Electrocardiographic diagnosis in patients with acute coronary syndrome].

Electrocardiographic role in a diagnosis of ischemic heart disease has still important value. As important electrocardiographic findings of myocardial ischemia, there are ST elevation or depression, increase high T wave (hyperacute T wave), negative T wave and negative U wave, but it is particularly important to compare those findings and manifestation. Because the patient can always carry it, event ECG is advantageous in that they can record electrocardiography by themselves when they have some symptom. It is necessary to have attention to what abnormal findings of the electrocardiogram which it is easy to be overlooked such as increase T wave or negative U wave appear in early stage of phase of acute coronary syndrome. When the patient has some symptom that acute coronary syndrome is thought about, it is necessary to record electrocardiograms on several times and to do follow up even if there is no electorcardiographic abnormalities at first recording.

White coat hypertension in centenarians.

BACKGROUND: To study white coat (WC) hypertension in centenarians, a cross-sectional surveillance was carried out on Uygurs, a long-lived population in China. METHODS: Twenty-four-hour ambulatory blood pressure (BP) monitoring (ABPM) was performed in 33 centenarians (age range, 100 to 113 years) and compared with 100 elderly subjects (age range, 65 to 70 years). All subjects were clinically healthy and capable of self-care. Subjects had no history, signs, or symptoms of cardiovascular disease and were receiving no medical treatments. Office BP, 24-h mean, daytime and night-time BP, pulse pressure, heart rate, standard deviation (SD), and coefficient of variation (CV) of the same variables were extracted from ABPM. The WC effect was defined as the difference between mean office and daytime BP. RESULTS: Centenarians demonstrated higher prevalence of WC hypertension, compared to elderly group (15% vs. 5%). The WC effect was also greater in centenarians than in elderly subjects, and was more marked for systolic BP than for diastolic BP and heart rate. The WC effect for systolic BP was positively correlated with both SD (r = 0.45, P < .01) and CV (r = 0.55, P < .01) for 24-h systolic BP in centenarians, but not in elderly subjects. CONCLUSIONS: Prevalence of WC hypertension was greater in centenarians than in elderly subjects. The WC effect and BP variation may be increased in centenarians. Previously observed higher BPs seen in very elderly individuals might be explained by the greater impact of WC hypertension.

Angiotensin-converting enzyme gene and longevity in the Xin Jiang Uighur autonomous region of China: an association study.

BACKGROUND: Longevity can be regarded as a multifactorial trait that results from an interaction between environmental factors and sets of epistatic alleles that have pleiotropic age-dependent effects. The Hotan district in the Xin Jiang Uighur Autonomous region of China is relatively isolated and is well known for an ethnic group that displays marked longevity. METHODS: We performed a correlation study between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and longevity by comparing distributions of the polymorphism between three different ethnic groups in this region. We obtained data from 424 subjects comprising 227 Uighur individuals, 108 Kazakh individuals, and 89 Han individuals. All subjects in the latter two groups ranged in age from 65 to 70 years, whereas the Uighur subjects actually comprised two different age groups: those ranging in age from 59 to 70 years (Uighur older group in Hotan [UOH]) and those ranging in age from 90 to 113 years (Uighur longevity group in Hotan [ULH]). Genomic DNA was extracted from peripheral white blood cells. Polymerase chain reaction was performed to amplify the I/D polymorphic region of the ACE gene. RESULTS: Frequencies of the insertion (I) and deletion (D) alleles were 0.596 (243/408) and 0.404 (165/408) in the Uighur group, 0.606 (130/216) and 0.394 (85/216) in the Kazakh group, and 0.657 (117/178) and 0.343 (61/178) in the Han group. The overall distributions of alleles in these three groups did not differ significantly (chi(2) = 4.6, p =.33). Within the Uighur group, frequency of the D allele was significantly higher in the ULH group (0.448) than in the UOH group (0.355) (p <.04). CONCLUSIONS: This association reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity. Our data may help elucidate the relationship between natural longevity and race difference among individuals in the Xin Jiang Uighur Autonomous region of China.

A novel variable number of tandem repeat polymorphism of the renin gene and essential hypertension.

The aims of the present study were to find new genetic markers of essential hypertension (EH) and to investigate relationships between EH and polymorphisms of the renin gene. Using single strand conformation polymorphism, we discovered a new variable number of tandem repeat (VNTR) polymorphism in intron 7 that is 18 bp upstream from the boundary with exon 8. Nucleotide sequencing revealed that this VNTR polymorphism is a tandem repeat of the 4-nucleotide sequence TCTG. There were 6 alleles of this VNTR polymorphism, ranging from 7 repeats to 12 repeats. We analyzed the association between EH and this VNTR polymorphism. There was no significant difference in the overall distribution of this VNTR polymorphism between the EH and normotensive subjects. In summary, we discovered a novel VNTR polymorphism in the renin gene, and this polymorphism was not associated with EH.

Time-series analysis of systolic blood pressure variation in thirty-three Uygur centenarians in China.

The Uygur are reported to have an unusually long life expectancy. The purpose of this research was to perform a time-series analysis of systolic blood pressure (SBP) variations in the Uygur and clarify the role of blood pressure variation (BPV) in their longevity. A cross-sectional survey was carried out in Hotan. We investigated 133 clinically healthy elderly Uygur subjects and divided them into two groups: 1) 33 Uygur centenarians in Hotan (UCH; aged > or = 100 years); and 2) 100 elderly Uygur in Hotan (UEH; aged 65-70 years). Blood pressure (BP) was monitored and analyzed with ambulatory BP monitoring. The frequency domain measures were obtained with the maximum entropy method. The mean 24-h SBP was higher in UCH than in UEH. The ratio of non-dipper type BPV was larger in the UCH than in UEH. The highest power spectral density occurred over a 12-h rather than a 24-h period in both UCH and UEH. Ultradian BPVs were more frequent in UCH than in UEH. The least square-fitting curves demonstrated that the maximum values, minimum values, and mean 24-h SBP values were higher in UCH than in UEH. The higher BP and greater number of ultradian BPVs in UCH may have been due to the greater energy expenditure for maintaining daily activities in this population. Factors such as meals, daytime naps, nocturnal micturition, decreased baroreceptor sensitivity, and arterial sclerosis may also have contributed to the higher ultradian BPVs. In conclusion, BPV in the 12-h is more dominant than in the 24-h in both UCH and UEH. BPVs in the 3-h and 4-h are more frequent in UCH than those in UEH.

A novel missense mutation of exon 3 in the type A human natriuretic peptide receptor gene: possible association with essential hypertension.

The natriuretic peptide (NP) family is involved in regulation of blood pressure and fluid volume. We recently characterized the exon/intron organization of the human type A NP receptor (hNPRA) gene. The aim of this study was to isolate the genetic markers according to the organization of this gene, and to study the association between this gene and essential hypertension. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we identified a novel missense mutation, M3411, consisting of a methionine (ATG) to isoleucine (ATC) substitution at nucleotide 1023 in exon 3. Computer-aided three-dimensional structural analysis suggested that M341 exists in the loop between two alpha-helices, and that the mutation may influence receptor activities by altering the conformation of the alpha-helices. We performed an association study of the mutation in 210 essential hypertension (EH) patients and 210 normotensive controls. The overall distribution of alleles was not significantly different between the control and EH groups. However, the C/C homozygous genotype was found only in the EH group. The ratio of plasma brain natriuretic peptide (BNP)/mean blood pressure of the C/C genotype was significantly higher than that of the G/G genotype or the G/C genotype. We conclude that the significance of homozygous M3411 mutation in exon 3 is worth investigating for its possible association with EH.