Association study between a novel single nucleotide polymorphism of the promoter region of the prostacyclin synthase gene and essential hypertension.

The purpose of this study was to investigate whether an association exists between the promoter region of the prostacyclin synthase gene and essential hypertension (EH). Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a novel single nucleotide polymorphism (SNP), T-192G, in the 5'-flanking region. We performed an association study using the SNP in 200 patients and 200 controls. The allele frequency distribution in the two groups was not significantly different. Thus, this SNP in the PGIS gene is not associated with EH.     

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.     

In vivo assessment of the electrophysiological integration and arrhythmogenic risk of myocardial cell transplantation strategies

Cell replacement strategies are promising interventions aiming to improve myocardial performance. Yet, the electrophysiological impact of these approaches has not been elucidated. We assessed the electrophysiological consequences of grafting of two candidate cell types, that is, skeletal myoblasts and human embryonic stem cell-derived cardiomyocytes (hESC-CMs). The fluorescently labeled (DiO) candidate cells were grafted into the rat's left ventricular myocardium. Two weeks later, optical mapping was performed using the Langendorff-perfused rat heart preparation. Images were obtained with appropriate filters to delineate the heart's anatomy, to identify the DiO-labeled cells, and to associate this information with the voltage-mapping data (using the voltage-sensitive dye PGH-I). Histological examination revealed the lack of gap junctions between grafted skeletal myotubes and host cardiomyocytes. In contrast, positive Cx43 immunostaining was observed between donor and host cardiomyocytes in the hESC-CMs-transplanted hearts. Optical mapping demonstrated either normal conduction (four of six) or minimal conduction slowing (two of six) at the hESC-CMs engraftment sites. In contrast, marked slowing of conduction or conduction block was seen (seven of eight) at the myoblast transplantation sites. Ventricular arrhythmias could not be induced in the hESC-CM hearts following programmed electrical stimulation but were inducible in 50% of the myoblast-engrafted hearts. In summary, a unique method for assessment of the electrophysiological impact of myocardial cell therapy is presented. Our results demonstrate the ability of hESC-CMs to functionally integrate with host tissue. In contrast, transplantation of cells that do not form gap junctions (skeletal myoblats) led to localized conduction disturbances and to the generation of a proarrhythmogenic substrate.     

Association study between the variants of the human ANP gene and essential hypertension.

Variants of atrial natriuretic peptide (ANP) are reported to be more common in blacks with hypertension than in normotensive controls and constitute an independent risk factor for cerebral infarction. The purpose of the present study was to investigate the role of ANP in the pathogenesis of essential hypertension (EH) in the Japanese. We investigated 2 previously reported ANP gene markers, G1837A and T2238C, for their possible associations with EH. A total of 233 individuals with EH and 213 age-matched normotensive (NT) control subjects were studied. The frequencies of the G and A alleles were 0.09 (42/466) and 0.91 (424/466), respectively, for the NT group and 0.11 (47/426) and 0.89 (379/426), respectively, for the EH group. These frequencies did not differ significantly between the two groups. The frequencies of the T and C alleles were 0.024 (11/466) and 0.97 (455/466), respectively, for the NT group and 0.03 (13/426) and 0.97 (413/426), respectively, for the EH group. These frequencies also did not differ significantly between the two groups. Neither G1837A nor the T2238C polymorphism of the ANP gene was associated with EH. Our findings do not support the hypothesis that the G1837A and T2238C polymorphisms of the ANP gene are markers for EH in the Japanese.     

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.     

A T1083C polymorphism in the human adenosine A2a receptor gene is not associated with essential hypertension

The adenosine A2a receptor (A2aAR) gene is thought to be involved in essential hypertension because adenosine elicits vasodilation and decreases arterial blood pressure via this receptor, and because disruption of the A2aAR gene increases blood pressure in mice. Therefore, using a restriction fragment length polymorphism (RFLP) of the A2aAR gene, we performed an association study in patients with essential hypertension. One hundred forty-two patients with essential hypertension and 142 age-matched subjects with normal blood pressure were studied. Polymerase chain reaction (PCR) was applied to amplify the T1083C polymorphic site in the A2aAR gene, and restriction analysis of the PCR product was employed to score the T and C alleles. Overall distributions of allele frequencies in the two groups were not significantly different. Thus, the alleles detected by this RFLP polymorphism in the A2aAR gene are not associated with essential hypertension.     

5-羟色胺转运体基因多态性与焦虑相关人格特质

5-羟色胺转运体（5-HTT）基因是个体间人格遗传差异和易发生多种精神障碍的一个最有前景的候选基因。该基因多态性通过影响基因转录而影响其功能,参与焦虑相关人格特质的调节。本文就 5-HTT基因与焦虑相关人格特质的关系及其研究进展作一综述。