Association of aldosterone synthase (CYP11B2) gene -344T/C polymorphism with essential hypertension in Mongolian nationality / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the -344T/C polymorphism of aldosterone synthase (CYP11B2) gene and essential hypertension in Chinese Mongolian population.</p><p><b>METHODS</b>By cluster-sampling method, a total of 1575 Mongolian people in Tongliao city of Inner Mongolia were included in this study. And 417 subjects were normotension, 596 subjects were prehypertension and 562 subjects were essential hypertension. A survey was conducted to collect data by personal interview using a standard questionnaire, meanwhile fasting blood samples were drawn. Height, weight, waist circumference, blood pressure, blood-fat indexes and fasting plasma glucose were measured. The variant genotypes of CYP11B2 were identified by PCR assays. The relationship between the -344T/C polymorphism of CYP11B2 gene and essential hypertension were analyzed by multinomial logistic regression model.</p><p><b>RESULTS</b>Crude prevalence of prehypertension among Mongolian people was 37.84% (596/1575) and hypertension was 35.68% (562/1575). The age-standardized prevalence of prehypertension was 38.57% and hypertension was 31.53%. The frequency of the T and C allele was 0.66 (481/728) and 0.34 (247/728) for normotension group, 0.69 (696/1042) and 0.33 (346/1042) for prehypertension group, 0.71 (706/998) and 0.29 (292/998) for hypertension group. The multiple logistic models showed CYP11B2 variant genotypes were associated with prehypertension (TT/CC, OR = 1.33, 95%CI: 0.87 - 2.01; TC/CC, OR = 1.74, 95%CI: 1.13 - 2.67; TC + TT/CC, OR = 1.49, 95%CI: 1.01 - 2.22); CYP11B2 variant genotypes were associated with hypertension (TT/CC, OR = 1.70, 95%CI: 1.07 - 2.70; TC/CC, OR = 1.59, 95%CI: 0.98 - 2.50; TC + TT/CC, OR = 1.66, 95%CI: 1.06 - 2.58).</p><p><b>CONCLUSION</b>CYP11B2 gene -344T/C polymorphism were associated with essential hypertension in Chinese Mongolian population.</p>

Impact of gene-environment interaction between the C (-344) T polymorphism of CYP11B2 and drinking index on the risk of hypertension under multifactor dimensionality reduction model in Chinese Mongolian population / 中华流行病学杂志

1.22-4.56), 2.05(1.07-3.94) and 5.56(2.54-12.18) respectively. Conclusion Essential hypertension might positively be affected by the interaction of the C (-344) T polymorphism of CYP11B2 and the drinking index in Chinese Mongolian population.

Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality Chinese / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese.</p><p><b>METHODS</b>A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis.</p><p><b>RESULTS</b>The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects.</p><p><b>CONCLUSION</b>Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.</p>

Identification of a regulatory single nucleotide polymorphism in the adiponectin (APM1) gene associated with type 2 diabetes in Han nationality / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To identify the genetic defects of the the adiponectin (APM1) gene that contribute to the development of type 2 diabetes (T2DM) and determine the functional single nucleotide polymorphisms (SNPs) in the APM1 gene associated with T2DM in Han nationality.</p><p><b>METHODS</b>The APM1 gene 5'-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance (IGT) and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically assessed.</p><p><b>RESULTS</b>Three SNPs were identified in the APM1 gene 5'-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls (G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03). Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-L1 cell line.</p><p><b>CONCLUSION</b>SNP -11377 G/C in the proximal promoter region of the APM1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.</p>

Relationship between aldosterone synthase gene (CYP11B2) polymorphisms and essential hypertension in a northern Chinese Han population / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the relationship between genetic polymorphisms of C-344T in the promoter region and K173R in the exon 3 of aldosterone synthase gene (CYP11B2) and the incidence of essential hypertension in a northern Chinese Han population.</p><p><b>METHODS</b>We conducted a case-control study including 182 hypertensive patients and 189 healthy controls in Harbin newspaper office and assayed the genotypes of C-344T and K173R using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing technology.</p><p><b>RESULTS</b>The distributions of C-344T and K173R genotype frequencies in men and women were in accordance with the Hardy-Weinberg equilibrium. The differences of C-344T allele and genotype as well as K173R allele frequency distributions between hypertensive patients and healthy controls were not statistically significant in men and women and pooled population (P > or = 0.05). The difference of K173R genotype frequency distribution reached borderline significance (P = 0.0500) and was more pronounced in women (P = 0.0038) according to the dominant mode of inheritance. Moreover, the magnitude of this mode of inheritance was more remarkable after the confounding factors were adjusted. K173R statistically correlated with the systolic hypertension in women.</p><p><b>CONCLUSION</b>The CYP11B2 K173R polymorphism correlates with the susceptibility of essential hypertension in the northern Chinese Han population.</p>

Multiple risk factor clustering and risk of hypertension in the Mongolian ethnic population of China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate whether the clustering of risk factors, both environmental and genetic, increases the risk of essential hypertension (EH) and the accumulation of risk factors influences the blood pressure level in normotensives.</p><p><b>METHODS</b>On the basis of a prevalence survey, 501 subjects of Mongolian ethnicity (243 hypertensives and 258 normotensives) who were not related to each other were selected to conduct a case-control study. All subjects were interviewed with questionnaires and their blood specimens were collected. Renin gene insertion/deletion (I/D) polymorphism, a new genetic marker, was genotyped with PCR and polyacrylamide gel electrophoresis.</p><p><b>RESULTS</b>Overweight, alcohol consumption, and renin gene I/D polymorphism were significant risk factors of EH (P<0.05). The odds ratios (OR) for the number of risk factors were 2.39 (95%CI: 0.98-6.74) for one risk factor, 5.03 (95%CI: 2.06-14.18) for two, and 6.09 (95%CI: 1.85-22.38) for three respectively after adjusting for age and sex. In normotensives, age- and sex-adjusted mean blood pressures increased with more accumulation of risk factors. However, there were no significant differences among the different blood pressure levels according to the number of risk factors (P>0.05).</p><p><b>CONCLUSION</b>Overweight, alcohol consumption, and renin gene I/D polymorphism are risk factors of EH in the Mongolian ethnic population of China. The accumulation of the risk factors causes a sharp increase of the risk of EH.</p>

Association of angiotensin converting enzyme gene I/D polymorphism with type 2 diabetes mellitus / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with type 2 diabetes mellitus (T2DM).</p><p><b>METHODS</b>Two hundred and nine patients with T2DM diagnosed based on the criteria for diabetes mellitus in 1999 by WHO and 221 controls were recruited from general population of Dongcheng District in Beijing. All subjects were genotyped for the I/D polymorphism of ACE gene by PCR-fragment length polymorphism (FLP) assay. Blood pressure, levels of plasma glucose, lipids and serum insulin were determined. Body mass index (BMI), waist-hip ratio (WHR) and homeostasis model assessment-insulin resistance index (HOMA-IR) were calculated.</p><p><b>RESULTS</b>The genotype frequencies for ACE genes DD, ID, and II were 19.1%, 42.1%, and 38.8% in patients, respectively, and 9.6%, 49.4%, and 41.0% in controls, respectively. The ACE DD genotype frequency was significantly higher in patients than in controls (chi2 = 7.61, P = 0.022). Multivariate logistic regression analysis showed that the ACE DD genotype was a risk factor for T2DM, with the OR of 2.35 (95% CI 1.17-4.71) adjusted for age, sex, BMI, WHR, blood pressure, and serum cholesterol levels.</p><p><b>CONCLUSION</b>The ACE DD genotype is associated with the increased susceptibility to type 2 diabetes mellitus.</p>

Comparative study of APOB gene 3'VNTR polymorphisms between natural longevity and controls in Uighur nationality / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of polymorphisms in the apolipoprotein B gene (APOB) 3'variable number of tandem repeat with natural longevity in the Xinjiang Uighur nationality people.</p><p><b>METHODS</b>Totally 191 healthy individuals over 90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur population, the nationality, gender and living area were matched. Genotyping was performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and PCR-sequencing.</p><p><b>RESULTS</b>Fourteen alleles were found in the Xinjiang Uighur nationality population. The frequency of HVE36 and HVE42 in the natural longevity group were significantly higher than that in the control group (both P<0.05) and HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group. However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the natural longevity group compared to the control group. Logistic regression analyses revealed that allele L and the genotypes LL were positively associated with age, whereas the allele S and genotype SS were negatively associated with age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by PCR-sequencing.</p><p><b>CONCLUSION</b>These results indicate that the S allele, and SS genotype are frail factors in China Uighur natural longevity people, whereas allele L and genotypes LL are protective factors.</p>

Susceptible genes of essential hypertension / 中国医学科学院学报

Essential hypertension (EH) is a complex multifactorial disorder with genetic and environmental factors contributing to its prevalence. The genetic features have been revealed from the significant familial aggregation and the consistency among twins. Therefore, identification of EH susceptibility genes will be helpful to understand the pathophysiology of the disease, identify populations with potential risks of developing the disease, and select antihypertensive drugs. The present article introduces the search strategies of EH susceptibility genes and some genetic variants related to EH; meanwhile, it tries to analyze the difficulties and the role for samples in identifying susceptibility genes to EH.

Polymorphism of apolipoprotein E gene and natural longevity in the Xinjiang Uighur people: an association study / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the distribution of polymorphisms of apolipoprotein E(apoE) gene and its relation to natural longevity in the Xinjiang Uighur people.</p><p><b>METHODS</b>Using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP), the authors obtained data from centenarians(n=42), 90-year-old people (n=102), 65-70-year-old people (n=70) and controls(n=53).</p><p><b>RESULTS</b>The frequencies of apoE genotypes epsilon 3/4, epsilon 3/3 and epsilon 2/3 were 2.4%, 69.0% and 23.8% respectively in the centenarian group, and the frequencies of their epsilon 4, epsilon 3 and epsilon 2 alleles were 1.2%, 82.1% and 16.7%. The frequencies of genotype epsilon 3/4 and epsilon 4, epsilon 3 allele in the centenarian group were significantly lower than those in controls(P< 0.01), whereas the frequencies of genotype epsilon 2/3 and epsilon 2 allele in the centenarian group were significantly higher than those in controls(P< 0.01). Longevity was noted to be positively correlated with epsilon 2 and negatively correlated with epsilon 4.</p><p><b>CONCLUSION</b>This relationship reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity.</p>

Beta2-adrenergic receptor gene polymorphism in Chinese Northern asthmatics / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate whether the polymorphisms of beta2-adrenergic receptor (beta2-AR) at position 16, 27, 164 are associated with asthma in Northern Chinese subjects.</p><p><b>METHODS</b>Genomic DNA was collected from unrelated Northern Chinese population of Han ethnicity, including 125 unrelated asthmatic individuals and 96 healthy controls. Beta2-AR genes at position 16, 27, 164 were amplified by using restriction fragment length polymorphism (RFLP) and allelic specific polymerase chain reaction methods. All asthmatics had their serum IgE (total and specific) antibody or skin-prick test measured, bronchial reactivity to methacholine (Mch) and bronchial reversibility by beta2-agonist evaluated.</p><p><b>RESULTS</b>(1) The frequency of Gly 16 homozygous was significantly higher in the asthmatic group than that in healthy controls (22.4% vs. 8.3%, P < 0.05), OR was 2.9 with 95% CI 1.26-6.78. The proportion of Gly 16 allele was also higher in asthmatics than that in control (0.46 vs. 0.36, P < 0.05); Gly16 homozygous was not independently associated with asthma pathogenesis (P = 0.21, OR 0.42 with 95% CI 0.11-1.61). (2) Of 51 night attack patients, 18 carrying Gly16 homozygosity, if compared with 10 of 74 nonnocturnal asthmatics carrying this genotype, there was significant difference between these two groups (35.3% vs. 13.5%, P < 0.01). (3) The average dose of PD20-Mch was significantly lower in patients carrying Gln 27 homozygous than those carrying homozygous Glu 27 and Gln/Glu 27 heterozygous (0.2 +/- 0.3, 1.6 +/- 0.8, and 2.1 +/- 3.0 micromol/L, P < 0.05).</p><p><b>CONCLUSION</b>Beta2AR gene polymorphisms might confer susceptibility to asthma in Chinese Northern patients. Beta2-AR gene, coordinated with other candidate loci, plays a role in the development of asthma.</p>

Interaction and relationship between angiotensin converting enzyme gene and environmental factors predisposing to essential hypertension in Mongolian population of China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the association of specific functional gene ACE (I/D) variants of the renin-angiotensin system with essential hypertension (EH) and interaction between ACE (I/D) gene and risk factors for EH in a genetically homogenous Mongolia rural population of China.</p><p><b>METHODS</b>Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region.</p><p><b>RESULTS</b>The association was found between ACE genotype DD plus ID and EH, with an interaction between ACE genotype DD plus ID and cigarette smoking in an additive model. Cigarette smoking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 7.10 to 1.16. Interaction between ACE genotype DD plus ID and alcohol drinking on EH appeared an additive model. Alcohol drinking index and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 1.66 to 1.09. BMI and ACE gene showed a low exposure-gene (LEG) effect on EH, with interaction indices from 6.15 to 2.49. Interactions between ACE genotype and WHR on EH showed a multiplicative model. In a short,there was an interaction between ACE gene and cigarette smoking, alcohol drinking and BMI on EH, especially in a low dose-exposure effect</p><p><b>CONCLUSION</b>It is important for individuals who carry ACE D allele gene to prevent EH, and furthermore, to prevent and control coronary heart disease, in a view of population-based prevention.</p>

Polymorphisms of renin-angiotensin system in essential hypertension in Chinese Tibetans / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the potential implications of the genetic variability of angiotensin converting enzyme, angiotensinogen and angiotensin II type 1 receptor gene for essential hypertension in Tibetan.</p><p><b>METHODS</b>A case-control study was conducted in 173 hypertensive individuals and 193 individuals with normal blood pressure. Multiple logistic regression analyses were used to estimate the risks of developing hypertension for different genotypes, and haplotype analyses of the angiotensinogen gene were used to determine the association between two-locus angiotensinogen gene polymorphisms and hypertension.</p><p><b>RESULTS</b>As to the risk to high blood pressure and high systolic pressure, women with MM genotype were 7.7 (95% CI: 1.3-20.5) and 8.7 (95% CI: 1.8-20.1) times higher than those with TT genotype after adjustment for age and body mass index. Haplotype frequencies for M235T and G-6A were significantly different between hypertensive individuals and controls, which indicated an association of angiotensinogen gene haplotypes with hypertension, and a significant association of 235T/-6A haplotype with hypotensive effect.</p><p><b>CONCLUSION</b>Our results suggest that angiotensinogen gene 235MM is a predictor for hypertension development in Tibetan women but not in men, and may exert its hypertensive effect on linkage disequilibrum with a possible function locus of G-6A.</p>

A1166C polymorphism of the angiotensin II type 1 receptor gene and essential hypertension in Han, Tibetan and Yi populations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To clarify whether A1166C polymorphism of the angiotensin II type 1 receptor (AT(1)R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China.</p><p><b>METHODS</b>This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in genomic DNA. The data were analyzed by ANCOVA, chi-square test, and multiple logistic regression.</p><p><b>RESULTS</b>In normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (chi-square=4.166, P=0.125). The frequency of the A1166 allele in Tibetan male hypertensives was significantly higher than that in normotensives (chi-square=11.46, P=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (P=0.465) or Yi (P=0.357) populations. Body mass index in the Han and Yi populations (P=0.0001), age in the Tibetan and Yi populations (P=0.0001), and AA genotype in the Tibetan male population (P=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (P=0.0040).</p><p><b>CONCLUSION</b>The A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT(1)R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT(1)R gene is probably not involved in the pathogenesis of essential hypertension in Han and Yi populations.</p>

Association of polymorphism of human beta 2-adrenergic receptor gene and bronchial asthma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate whether beta 2-adrenergic receptor gene (beta 2AR) polymorphism at position 16, 27, 164 is in association with asthma susceptibility or asthmatic phenotype (including nocturnal asthma, serum IgE level, bronchial responsiveness, the status of asthmatics).</p><p><b>METHODS</b>By using PCR-RFLP and allelic-specific PCR (ASP), the polymorphism of beta 2AR gene at position 16, 27, 164 in 125 Han origin asthmatics and 96 normal healthy controls with the same ethnic nearby Beijing region were genotyped. All patients had their serum total IgE (TIgE) measured by RAST, pulmonary ventilatory function assessed by FEV1% and FEV1/FVC, bronchial responsiveness challenged by methacholine (if FEV1% > 70%), and brocho-reversibity by inhaling beta 2-agonist.</p><p><b>RESULTS</b>There was higher prevalence of Gly16 homozygous of beta 2AR in asthmatics than that in normal healthy controls (22.4% vs 8.3%, P < 0.05), with odd ratio (OR) 2.918 (95% CI: 1.256-6.781); Also there was higher frequency of Gly16 homozygous of beta 2AR in nocturnal asthmatics than that in nonnocturnal asthmatics (35.3% vs 13.5%, P < 0.01), but Gly16 homozygous of beta 2AR was low an independent risk factor for the pathogenesis of asthma. The dose of methacholine was low in asthmatics carrying Gln27 homozygous beta 2AR than Glu27 homozygous beta 2AR and Gln/Glu27 heterozygous beta 2AR in brocho-challenge test [(0.205 +/- 0.275) vs (2.11 +/- 3.00) vs (1.575 +/- 0.828) mumol, P < 0.05].</p><p><b>CONCLUSIONS</b>Gly16 homozygous beta 2AR was associated with asthma susceptibility in Chinese patients with Han ethnic nearby Beijing region, and Gly16 homozygous beta 2AR was associated significantly with nocturnal asthma. Glu27 homozygous beta 2AR was related to hyper-bronchial reactivity of asthmatics.</p>