Correlation between plasma aldosterone concentration and left ventricular structure in hypertensive patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the correlation between plasma aldosterone concentration (PAC) and left ventricular structure in hypertensive patients.</p><p><b>METHODS</b>A total of 201 hypertensive patients [117 male, aged from seventeen to sixty eight years old, mean (43.6 ± 10.2) years] were included. All subjects underwent echocardiography examination for measurement of left ventricular end-diastolic dimension (LVEDD), LV posterior wall thickness (LVPWT), interventricular septum thickness (IVST) and LV mass index (LVMI). Plasma PAC was also measured at three postural positions. According to the sitting PAC, subjects were divided into high aldosterone group (PAC ≥ 120 ng/L, n = 83) and normal aldosterone (PAC < 120 ng/L, n = 118) group. Bivariate correlation and multiple stepwise regression analysis were performed to analyze the correlation between left ventricular structure parameters and PAC.</p><p><b>RESULTS</b>IVST, LVPWT values were significantly higher in the increased PAC group than that in normal PAC group [ (10.4 ± 1.0) mm vs. (10.9 ± 1.8) mm, (10.1 ± 0.7) mm vs.(10.4 ± 1.5) mm, all P < 0.05]. Bivariate correlation analysis showed that PAC was weakly correlated with IVST (r = 0.190, P < 0.05) , while was not correlated to LVMI, LVPWT and LVEDD (all P > 0.05). Multiple linear stepwise regression analysis showed that PAC was positively correlated with IVST and LVPWT (β = 0.206 and β = 0.241, respectively, all P < 0.05), but was not correlated to LVMI and LVEDD (all P > 0.05).</p><p><b>CONCLUSION</b>PAC is positively correlated with IVST and LVPWT in hypertensive patients.</p>

Relationship between genetic variation of furin and insulin resistance in Chinese Kazakh population / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the relationship between genetic variation of Furin and insulin resistance in Chinese Kazakh population.</p><p><b>METHODS</b>Based on a cross-sectional epidemiological study in a Chinese Kazakh population, a case-control study was conducted. All the sequence variants located promoter and exon regions of Furin were identified by directly sequencing of PCR product in 50 (25 males) individuals with insulin resistance, which were randomly chosen from the study population. The representative polymorphism was detected by TaqMan PCR in 861 subjects (366 males, 254 in case group and 607 in control group). The relationship between genetic variation of Furin and insulin resistance in this cohort was analyzed.</p><p><b>RESULTS</b>Twelve genetic variations in Furin were identified by sequencing 50 individuals with insulin resistance and 4 common SNPs (rs6226, rs6227, rs2071410, and rs4932178) were selected as representatives for genotyping in this Chinese Kazakh population. The rs6226, rs6227, rs2071410, and rs4932178 polymorphisms were successfully genotyped. The distribution of the genotypes of rs6226, rs6227, rs2071410, and rs4932178 polymorphism was similar between case and controls (all P > 0.05). The homeostasis model assessment for insulin resistance (HOMA-IR) levels was also similar among individuals with different genotypes (all P > 0.05).</p><p><b>CONCLUSION</b>The genetic variation of Furin is not associated with insulin resistance in this cohort of Chinese Kazakh population.</p>

Genetic polymorphism of six transmembrane protein of prostate 2 associated with diabetes mellitus in Xinjiang Uygur population / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the association between the genetic variations of six transmembrane protein of prostate 2 (STAMP2) with type 2 diabetes mellitus (T2DM) in Xinjiang Uygur population.</p><p><b>METHODS</b>A case-control study was conducted based on epidemiological investigation. A total of 1838 Uygur subjects were selected and divided into two groups: T2DM group (n=274) and control group (n=1564). All exons, flanking introns, and the promoter regions of STAMP2 gene were sequenced in 48 Uygur Xinjiang population with diabetes. Representative variations selected were genotyped by TaqMan-PCR method in all individuals.</p><p><b>RESULTS</b>Ten novel and 6 known variations in the STAMP2 gene were identified. The distribution of genotype rs8122 significantly differed between T2DM group and control group (P=0.05), whereas the distribution of genotypes rs1981529 and rs34741656 showed no such difference. The fasting insulin in the total cohort and homeostasis model of assessment index in females showed significant difference between these two groups (P<0.05), while the adjusted P value showed no statistical significance (P>0.05). In the male population, the different genotypes of rs8122 variation of STAMP2 gene were not significantly different (P>0.05).</p><p><b>CONCLUSION</b>Three polymorphisms (rs8122, rs1981529 and rs34741656) of STAMP2 gene may be not related with T2DM in Xinjiang Uygur population.</p>

Association between genetic polymorphism of the six-transmembrane protein of prostate 2 and obesity in Uygur / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between genetic variations of the six transmembrane protein of prostate 2 (STAMP2) and obesity in Xinjiang Uygur population.</p><p><b>METHODS</b>A total of 2332 Uygur subjects (1455 obesity and 877 non-obesity control subjects) were included in this case-control study based on epidemiological survey. Genetic variations of STAMP2 gene functional region were sequenced. The representative variations selected were genotyped by TaqMan-PCR method.</p><p><b>RESULTS</b>Twenty genetic variations, including 14 novel variations, were identified. The genotype distributions of the control group and obesity group were in the Hardy-Weinberg equilibrium (both P > 0.05). The frequency of AA of rs1981529 (67.6% vs. 62.8%, P < 0.05) and the frequency of G-A-G haplotype (62.4% vs. 58.9%, P < 0.05) in obesity group were significantly higher than that in controls while the frequency of A-G-G haplotype was significantly lower in the obesity patients than that in the control group (17% vs. 20%, P < 0.05). After adjusting age, sex, smoking and drinking, logistic regression analysis showed that the AA genotype of rs1981529 (OR: 1.276, 95%CI: 1.049 - 1.552; P < 0.05) and the G-A-G haplotype (OR: 1.356, 95%CI: 1.007 - 1.862, P < 0.05) were the independent risk factors for obesity in this cohort.</p><p><b>CONCLUSION</b>The AA genotype of rs1981529 and G-A-G haplotype are associated with obesity in Uygur population of Xinjiang.</p>

Association between GIRK4 gene polymorphisms and insulin resistance in Xinjiang Uygur population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between polymorphisms of protein-activated inwardly rectifying K+ channel (GIRK4) gene and insulin resistance (IR) in Xinjiang Uygur population.</p><p><b>METHODS</b>A cross-sectional epidemiological survey-based case-control study was carried out, for which 1295 subjects (including 324 IR patients and 971 non-IR controls) were randomly selected. Functional region of the GIRK4 gene was sequenced for 48 randomly selected IR patients. Representative variable sites were chosen, with its association with IR assessed in 1295 Uygur subjects.</p><p><b>RESULTS</b>rs11221497 variant was associated with IR in Uygur subjects under 50 years old (P=0.017 in genotype model, P=0.009 in dominant model). Subjects with dominant model of CC genotype have an OR of 1.833 (95%CI: 1.157-2.905) for IR.</p><p><b>CONCLUSION</b>GIRK4 gene polymorphisms may be associated with IR in Uygur ethnics from Xinjiang. The CC genotype of rs11221497 variant is a risk factor for IR.</p>

A common variation within the STEAP4 gene exons is associated with obesity in Uygur general population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Coordinated regulation of nutrient and inflammatory responses by six transmembrane epithelial antigen of prostate 4 (STEAP4) was essential for metabolic homeostasis. STEAP4 expression in human white adipose tissue was associated with obesity. This study aimed to evaluate association between STEAP4 genetic polymorphisms and obesity in Uygur Chinese general population.</p><p><b>METHODS</b>The functional regions of STEAP4 gene were sequenced in 96 Uygur with obesity (body mass index (BMI) > 30 kg/m²). Representative variations were selected according to the function and linkage disequilibrium and genotyped in 1507 obesity (BMI ≥ 25 kg/m²) and 825 non-obesity control (BMI < 25 kg/m²), all of whom were selected from epidemiology study of obesity-related diseases during January to February 2007 among Uygur population in Hetian area of Xinjiang Uygur Autonomous Region.</p><p><b>RESULTS</b>Fourteen novel and 6 known single nucleotide polymorphism (SNPs), including 2 nonsynonymous SNPs (nsSNPs), in the STEAP4 gene were identified. Of the 3 representative SNPs, the nsSNP rs1981529 (Gly75Asp, 224A/G) was significantly associated with obesity phenotype (additive P/Pc = 0.001/0.006, dominant P/Pc = 0.003/0.018, odds ratio (OR) and 95% confidence interval (CI) adjusted for age, gender and drinking 0.755 (0.641 - 0.890) and 0.750 (0.621 - 0.907), respectively). By the multiple linear regression analysis, the quantitative phenotypes of BMI (P/Pc = 0.002/0.004) and waist circumference (P/Pc = 0.004/0.008) were found to be significantly associated with the genotypes of rs1981529 (Gly75Asp, 224A/G) in Uygur general population, and effect size (beta value) of one allele G of rs1981529 (Gly75Asp, 224A/G) was - 0.553 kg/m² for BMI and - 1.311 cm for waist circumference after controlling age, gender and drinking factors.</p><p><b>CONCLUSIONS</b>The present study shows an association of the common variation rs1981529 (Gly75Asp, 224A/G) in the STEAP4 gene with obesity in Uygur general population. Further studies should replicate the results using larger populations.</p>

Association of genetic variations of the prostasin gene with essential hypertension in the Xinjiang Kazakh population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transgenic overexpression of human prostasin in rats disturbs salt balance and causes hypertension. We investigated whether genetic variations in prostasin were implicated in hypertension or related phenotypes in the Xinjiang Kazakh population.</p><p><b>METHODS</b>We sequenced all exons and the promoter regions of the prostasin gene in 94 hypertensive individuals, and the genotype identification was performed by the TaqMan polymerase chain reaction method. Case-control studies were conducted in 938 Kazakh subjects.</p><p><b>RESULTS</b>E342K and 2827G > A, which are novel variants, were successfully genotyped in the general Xinjiang Kazakh population with a sample size of 938 individuals (406 men and 532 women). Only one hypertensive patient was identified with the E342K mutation. No significant association was observed between 2827G > A and hypertension. However, quantitative traits of hypertensive intermediate phenotypes were significantly associated with the A allele; P = 0.041 and 0.034 for body mass index (BMI) in the additive and recessive models, P = 0.042 and 0.018 for OGTT-2h glucose in the additive and recessive models, P = 0.031 for IRT-3h insulin in the recessive model, and P = 0.038 for serum potassium in the dominant model.</p><p><b>CONCLUSIONS</b>This study does not provide evidence of a major role of prostasin variation in blood pressure modulation. However, association of prostasin polymorphisms with hypertension and metabolic effects can be observed in our population. Further investigation is warranted to clarify the relevance of prostasin polymorphisms to blood pressure regulation.</p>

Genetic variations of bone morphogenetic protein 7 gene are associated with hypertriglyceridemia of Uygur Chinese in Xinjiang / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the association between the genetic variations of functional region in bone morphogenetic protein (BMP7) gene and dyslipidemia in Chinese Uygur individuals.</p><p><b>METHODS</b>The case-control study was conducted in 1514 Uygur Chinese based on epidemiological investigation. The all exons, segmental introns and the promoter regions of BMP7 gene were sequenced in 48 out of 1514 Uygur Chinese. Representative variations were then selected according to the minor allele frequency (MAF) and linkage disequilibrium, and genotyped using the TaqMan polymerase chain reaction method in 1514 Uygur Chinese, a relatively isolated general population in a relatively homogeneous environment, to observe the association between genetic variations of BMP7 gene and dyslipidemia.</p><p><b>RESULTS</b>Five novel and eight known variations in the BMP7 gene were identified. All genotype distributions were tested for deviations from Hardy-Weinberg equilibrium. There were significant differences of genotype distribution of rs6025422 between hypertriglyceridemia group and control group (P = 0.001). The levels of triglyceride (TG) showed a decreasing tendency in individuals with AA, AG and GG genotypes of rs6025422. Odd ratio (OR) value adjusted for age, gender, body mass index, smoking and alcohol drinking habits was 0.562 by logistic regression analysis (95%CI: 0.393 - 0.802, P = 0.002).</p><p><b>CONCLUSION</b>The present study shows rs6025422 polymorphism in the BMP7 gene is linked with hypertriglyceridemia phenotype in Uygur Chinese population.</p>

Genetic variation and association of STEAP4 gene with metabolic syndrome in Chinese Uygur patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic variations of the six transmembrane epithelial antigen of prostate 4 gene (STEAP4) in Chinese Uygur patients with metabolic syndrome (MetS) and to analyze the association of the representative genetic variations of STEAP4 gene with MetS in the population.</p><p><b>METHODS</b>The sequences of STEAP4 gene functional region (all exons, exon-intron boundaries and the putative promoter region, including the -1 kb 5'and 3'untranslated regions) were amplified and sequenced for patients with MetS. The representative variations were selected based on the function (missense mutation) and linkage disequilibrxium (γ² > 0.8) and genotyped with TaqMan-PCR method in 1910 general populations (682 MetS and 1228 non-MetS controls). The subjects were selected from the cross-sectional study of obesity, hypertension, diabetes, dyslipidemia from January to February 2007 among Uygur people, a relatively isolated population with a relatively homogeneous environment, in Hextian area in Xinjiang Uygur Autonomous Region.</p><p><b>RESULTS</b>(1) Fourteen novel and six known single nucleotide polymorphisms (SNPs) or mutations, including 2 missense mutations, were identified at the functional region of STEAP4 gene in 96 Uygur patients with MetS. The minor allele frequencies of the SNPs of STEAP4 gene in Uygur population were different from that in European and Chinese Han in Beijing area. (2) The SNP 364G/A (rs34741656, Ala122Thr) was significantly associated with MetS [dominant model P = 0.034, OR = 0.757(95%CI: 0.584-0.982) adjusted for age and gender], and was associated with fasting blood glucose (FBG) (P = 0.049) and 2-hour postprandial glucose (2HPG) (P = 0.027) levels in controls. In this SNP, the AA carriers had lower blood glucose levels compared with subjects carrying GG and GT genotypes. (3) The common haplotype H4 (rs8122/rs1981529/ rs34741656, G-A-A), may be associated with MetS (permutation P = 0.089).</p><p><b>CONCLUSION</b>STEAP 4 genetic polymorphisms may be associated with MetS risk in Chinese Uygur population.</p>

Association of genetic variations of prostasin gene with the essential hypertension in Xinjiang Kazakhs / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the relationship between genetic variations of prostasin gene and essential hypertension (EH) in Xinjiang Kazakhs.</p><p><b>METHODS</b>Totally 938 Fukang City residents who were older than 30 years were enrolled in this study using cluster random sampling method. Standardized questionnaire and physical examination were performed. Among them there 451 EH patients (EH group) and 478 normotensive (NT) subjects (NT group) according to Guidelines of Prevention and Control for Hypertension in 2005. All the exons and promoter regions of prostasin gene were sequenced in 94 EH patients. Representative variations (297A>C, 2827C>T, and E342K) were genotyped using TaqMan polymerase chain reaction method in all 938 subjects. The frequencies of genotypes were compared between the EH and NT groups.</p><p><b>RESULTS</b>Ten variations were found as follows: -36G>C, -27C>T, 78G>A, 81G>C (rs8049043), 297A>C, 350C>T, 351A>C, 2827C>T, 3482G>A (E342K), and 3783A>G. E342K and 2827C>T were successfully genotyped. E342K mutation was identified in only one hypertensive patient. CC, CT, and TT genotypes existed in 2827C>T polymorphism. The frequencies of CC, CT, and TT were 81.0%, 17.3, and 1.7% in EH group and 80.3%, 18.9%, and 0.8% in NT group, respectively. The frequencies of C and T alleles were 89.6% and 10.4% in EH group and 89.8% and 10.2% in NT group, respectively. The distribution of genotypes and allele frequencies were not significantly different between these two groups (chi2=2.048, P=0.353 and chi2=0.001, P=0.973). Blood pressure was not significantly among subjects with these three genotypes (P>0.05).</p><p><b>CONCLUSIONS</b>The EH of Xinjiang Kazakhs is not associated with 2827C>T polymorphism in the prostasin gene. E342K mutation in the prostasin gene may contribute partly to the hypertensive phenotype in this population.</p>