A polymorphism of kynureninase gene in a hypertensive candidate chromosomal region is associated with essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To identify single nucleotide polymorphisms (SNP) in the regulatory and coding regions of human kynureninase (KYNU) gene in a hypertensive candidate chromosomal region 2q14-q23 of Han Chinese, and to investigate the relationship between polymorphisms in KYNU and essential hypertension.</p><p><b>METHODS</b>The SNPs in the promoter region and exons of the KYNU gene were detected by direct DNA sequencing. Genotyping of the nonsynonymous Lys412Glu (A/G) polymorphism was performed by DHPLC technology in 456 hypertensive patients and 430 normal controls.</p><p><b>RESULTS</b>Sixteen SNP were identified in the KYNU gene, including 6 in the regulatory region and 2 in the coding region (both of them lead to substitution of amino acid). Significant differences between hypertensive patients and normal controls were observed for the distribution of alleles (chi(2) = 6.693, P = 0.035) and genotypes (chi(2) = 4.188, P = 0.041) of the Lys412Glu polymorphism in all subjects, and for the distribution of alleles in the subgroup of men (chi(2) = 4.424, P = 0.035).</p><p><b>CONCLUSION</b>The Lys412Glu polymorphism of the KYNU gene in a hypertensive candidate chromosomal region is associated with essential hypertension in Han Chinese.</p>

Association of peripheral and central blood pressure with the alpha-adducin Gly460Trp polymorphism in a Chinese population / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association of peripheral and central blood pressure with the alpha-adducin Gly460Trp polymorphism in Chinese.</p><p><b>METHODS</b>We randomly selected 6 villages from JingNing County, ZheJiang Province. We invited nuclear families to take part in our study. We measured each participant's blood pressure at the non-dominant arm by means of a standard mercury sphygmomanometer at subjects' homes. Five consecutive readings were averaged for analysis. Central blood pressures were obtained by use of SphigmoCor pulse wave analysis system. The observers administered a standardized questionnaire to collect information on smoking habits, alcohol consumption and use of antihypertensive drugs. Venous blood was sampled and the adducin genotype was determined by restrictive fragment length polymorphism (RFLP).</p><p><b>RESULTS</b>Four hundred and forty-two subjects included 230 (52.0%) women, and 116 (26.2%) hypertensive patients, of whom 49 (11.1%) took antihypertensive drugs. The frequencies of alpha -adducin GlyGly, GlyTrp and TrpTrp genotypes were 21.3%, 54.5% and 24.2%, respectively. There was no association between the alpha-adducin Gly460Trp polymorphism and peripheral systolic and diastolic blood pressure and pulse pressure. However, both before and after adjustment for sex, age, age(2), body-mass index, current smoking, alcohol intake, and antihypertensive treatment, the alpha-adducin polymorphism was significantly (P < 0.02) associated with central systolic blood pressure and central pulse pressure. After adjustment, central systolic blood pressure (+/- SE) averaged 122.5 +/- 3.5, 114.1 +/- 1.5 and 109.1 +/- 1.8 mm Hg (P = 0.01) in the GlyGly, GlyTrp and TrpTrp subjects, respectively. The corresponding values for central pulse pressure were 39.4 +/- 1.3, 36.4 +/- 1.0 and 32.9 +/- 0.9 mm Hg (P = 0.002), respectively.</p><p><b>CONCLUSIONS</b>In the JingNing population, the adducin 460Trp allele was associated with lower levels of central systolic pressure and pulse pressure.</p>

No association between 3 polymorphisms of transforming growth factor beta3 gene and essential hypertension in Chinese / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate possible association between the single nucleotide polymorphisms (SNPs) of transforming growth factor beta3 (TGF-beta3) gene and essential hypertension (EH) in Chinese.</p><p><b>METHODS</b>The promoter region, exons, as well as part of the introns of TGF-beta3 gene were sequenced by a fluorescent labeling automatic sequencing method to detect and characterize the SNPs in 24 DNA samples from a Chinese population. Then we conducted a case-control study using 396 patients with hypertension (case) and 214 nomortensive subjects (control). The three SNPs including Thr63Asn, SS5608219 and SS5608220 were genotyped by PCR-RFLP or real-time allele-specific PCR in subjects studied.</p><p><b>RESULTS</b>Seven SNPs in the exons, introns and 3'untranslated region (3'UTR) of TGF-beta3 gene were identified. Among them, 2 SNPs were found to be novel genetic variants and one of the two located in the exon 1 and produced substitution of amino acid. However, no differences were found between hypertensives and nomortensives in genotype distribution and allele frequency of SS5608219, Thr63Asn or SS5608220 polymorphisms.</p><p><b>CONCLUSIONS</b>Two novel SNPs of TGF-beta3 gene were identified in Chinese. One of them produces a threonine to asparagines substitution in codon 63 (Thr63Asn). But no association was found between TGF-beta3 gene polymorphisms and EH in Chinese.</p>

Association of single nucleotide polymorphism in human SCN7A gene with essential hypertension in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the single nucleotide polymorphisms (SNPs) in the regulatory and coding regions of human SCN7A (sodium channel, voltage-gated, type VII, alpha polypeptide) gene and to investigate the association of some of these SNPs with essential hypertension (EH) in Chinese.</p><p><b>METHODS</b>The promoter region, exons, as well as part of the introns of SCN7A gene were sequenced by a fluorescent labeling automatic sequencing method to identify and characterize the SNPs in Chinese population. SNP genotyping was performed by PCR-RFLP or direct DNA sequencing in unrelated EH patients and normotensive controls from a Chinese Han population residing in Shanghai area. Case-control studies on seven SNPs were first carried out in 96 patients and 96 normotensive controls. The positive finding was further verified in an extended study containing 288 patients and 288 controls.</p><p><b>RESULTS</b>Thirty-two SNPs were identified through a 13,132 bp sequencing of SCN7A gene. Among them, seven were in regulatory region, ten in coding regions, one in 3'UTR and fourteen in introns. Thirty SNPs were novel SNPs, and a cSNP in exon 18 (SNP021) was associated with hypertension.</p><p><b>CONCLUSION</b>The SNP021 in the gene SCN7A is associated with essential hypertension of Chinese Han population in Shanghai and the role of SCN7A gene in hypertension deserves to be further analyzed.</p>

Activation of nucleus-independent signals triggered by N-methyl-N'-nitro-N- nitrosoguanidine / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the effect of MNNG on inducement of non-targeted mutation and activation of several cellular signal transduction pathways, and to determine whether the activation of these signaling pathways was dependent on the DNA-damage.</p><p><b>METHODS</b>Vero cells were enucleated by discontinuous density centrifugation. The PKA activities were measured by enzyme-linked immunosorbent assay. The status of cell membrane receptors was studied with immunofluorescent staining and confocal microscopy.</p><p><b>RESULT</b>In enucleated cytoplasts, MNNG-treatment increased PKA activity for about 2.3-fold in accordance with the 2.7-fold up-regulation of PKA activity in whole vero cells exposed to MNNG. The clustering of cell surface receptors of epidermal growth factor and tumor necrosis factor alpha was also observed in cells exposed to MNNG; this phenomenon was also found in enucleated cells.</p><p><b>CONCLUSION</b>The results indicate that the initiation of signal cascades induced by low concentration of MNNG might be associated with its interaction with cell surface receptors and/or direct activation of related signal proteins but not its DNA damage.</p>

Activation of transcription factors induced by low concentration of N-methyl-N'-nitro-N-nitrosoguanidine / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of MNNG on some of the transcription factors such as NF- kappaB, CREB, AP-1 and c-Myc.</p><p><b>METHODS</b>The activities of these transcription factors were measured by transient transfection assay of SEAP vectors.</p><p><b>RESULT</b>The expressions of AP-1, CREB and NF- kappaB driven reporter genes were elevated for about 1.3, 1.4 and 1.3 times in MNNG-treated cells, respectively, as compared to untreated controls. However, the exposure of MNNG had no effect on the activity of c-Myc.</p><p><b>CONCLUSION</b>The activation of certain transcription factors might be involved in the process of untargeted mutation induced by low concentration of MNNG treatment.</p>