Iron-catalyzed arylalkoxycarbonylation of N-aryl acrylamides with carbazates.

A novel arylalkoxycarbonylation of N-aryl acrylamides with carbazates leading to alkoxycarbonylated oxindoles has been developed. The reported reactions employ economical and environmentally benign FeCl2·4H2O as a catalyst and easily accessible and safe carbazates as alkoxycarbonyl radical precursors.

Iron halide-mediated regio- and stereoselective halosulfonylation of terminal alkynes with sulfonylhydrazides: synthesis of (E)-ß-chloro and bromo vinylsulfones.

Halosulfonylation of terminal alkynes was achieved with sulfonylhydrazides as the sulfonyl precursor and inexpensive iron halide as halide source in the presence of TBHP, allowing the regio- and stereoselective generation of (E)-ß-chloro and bromo vinylsulfones.

Association of the renin gene polymorphism, three angiotensinogen gene polymorphisms and the haplotypes with essential hypertension in the Mongolian population.

Renin is a rate-limiting enzyme of the renin-angiotensin system and plays a crucial role in the regulation of blood pressure (BP). Angiotensinogen (AGT) is the precursor of potent vasoactive hormone angiotensin II and the AGT gene has been incriminated as a marker for genetic predisposition to essential hypertension (EH) in some ethnic groups. The purpose of the study is to explore the association of a new genetic marker of renin gene, and AGT gene M235T, A-6G, and A-20C polymorphisms and their haplotypes with EH in the Mongolian population. On the basis of the prevalence survey, 243 hypertensives and 258 normotensives who had no blood relationship with each other were selected as subjects. All the subjects were interviewed with questionnaires and their blood specimens were collected. Renin gene insertion/ deletion (I/D) polymorphism was genotyped by PCR-polyacrylamide gel electrophoresis. AGT gene M235T, A-6G, and A-20C polymorphisms were genotyped by a PCR-restriction fragment length polymorphism and single-strand conformation polymorphism. The frequencies of renin genotype DD and allele D in hypertensives (36.21%, 63.79%, respectively) were significantly higher than those in normotensives (29.84%, 57.17%, respectively, P < 0.05). The odds ratios (OR) of renin genotype ID, DD to renin genotype II on hypertension were 1.98 (OR 95% CI 1.08-3.72) and 2.51 (OR 95% CI 1.33-4.88), respectively. There were no significant differences in the distributions of genotypes and alleles for AGT gene M235T, A-6G, and A-20C polymorphisms and all different haplotypes between the two groups. Renin gene I/D polymorphism is associated with EH, whereas AGT gene M235T, A-6G, and A-20C polymorphisms and the haplotypes are not associated with EH in the Mongolian population.

Endothelial nitric oxide synthase gene polymorphisms associated with susceptibility to high altitude pulmonary edema in Chinese railway construction workers at Qinghai-Tibet over 4 500 meters above sea level / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To examine whether the polymorphisms of endothelial nitric oxide synthase (eNOS) gene are associated with the susceptibility to high altitude pulmonary edema (HAPE) in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level.</p><p><b>METHODS</b>A case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat (VNTR) in intron 4, were genotyped using polymerase chain reaction (PCR) and confirmed with DNA sequencing.</p><p><b>RESULTS</b>The frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group (P=0.0028 and P=0.0047, respectively). However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes (H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR) were significantly higher in HAPE patients (both Pü0.0001). On the contrary, the frequencies of H1 (T-G-b) and H2 (T-G-a) were lower in HAPE patients than in healthy controls (both Pü0.001).</p><p><b>CONCLUSIONS</b>Two haplotypes (T-T-b and C-G-a) may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.</p>

Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur nationality.

This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, Xbal-RFLP, VNTR) and natural longevity persons among the Uygur people in Xinjiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65-70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+ X+ genotype, M and L alleles and the genotypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X-and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possible protective factors for the naturally long-lived Uygur people in China.

Multiple risk factor clustering and risk of hypertension in the Mongolian ethnic population of China.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Polymorphism of apolipoprotein E gene and natural longevity in the Xinjiang Uighur people: an association study].

OBJECTIVE: To explore the distribution of polymorphisms of apolipoprotein E(apoE) gene and its relation to natural longevity in the Xinjiang Uighur people. METHODS: 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). RESULTS: 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. CONCLUSION: This relationship reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity.

[Polymorphism of angiotensin converting enzyme gene and natural longevity in the Xinjiang Uygur people: an association study].

OBJECTIVE: To explore the distribution of I/D polymorphisms of angiotensin converting enzyme (ACE) gene and its relation to natural longevity in the Xinjiang Uygur people. METHODS: Polymerize chain reaction, single strand conformation polymorphism, and direct sequencing technique were used to test the I/D polymorphisms of ACE gene in 42 centenarians, 102 people aged 90-99, 70 people aged 65-70, 53 cases of natural death aged 65-70 were used as controls. RESULTS: The frequencies of ACE genotypes DD, DI, and II were 28.6%, 30.9%, and 40.5% respectively in the centenarian group, the frequency rates of D and I alleles were 0.44 and 0.56. The frequency rate of D/D genotype of the centenarian group was significantly higher than that of the group aged 65-70 (28.6% vs. 12.9%, chi2 = 4.25, P < 0.05), however, not significantly different from that of the group aged 90 (P > 0.05). The frequency rate of D allele of the group of centenarian was significantly higher than that of the group aged 65-70 (44.0% vs. 36.4%, chi2 = 4.47, P < 0.05). The frequency rates of genotype D/D and D alleles were significantly higher in the centenarian group than in the controls (both P < 0.01). CONCLUSION: ACE gene polymorphism is closely correlated with life span of individuals. Longevity is the result of pleiotropic age-dependent influence of multiple factors.

Interaction and relationship between angiotensin converting enzyme gene and environmental factors predisposing to essential hypertension in Mongolian population of China.

OBJECTIVE: 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. METHODS: Individuals (n=1099) were recruited from general population of Kezuohouqi Banner in Inner Mongolian Autonomous Region. RESULTS: 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 CONCLUSION: 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.

[Genetic basis of essential hypertension in Tibetan].

OBJECTIVE: To explore the role genetic factor plays in the pathogenes is of essential hypertension (EH) among Tibetans and to investigate whether angiotensinogen (AGT) is involved in the pathogenesis of EH. METHODS: A case-control association study was conducted among 353 essential hypertensive subjects and 317 genealogic structure-matched normotensive controls, all of Tibetan nationality. The correlation between polymorphism of M235T and 6A-->G variant in AGT gene and EH susceptibility in Tibetans was examined by polymerase chain reaction ( PCR) and PCR/RFLP (restriction fragment lengths polymorphism) with AspI and BstN I,respectively. RESULTS: (1) The affection rate of EH among the first-degree relatives of Tibetan EH proband was 43.3%. The heritability of EH was 77.2% +/- 13.3% by Falconer method. (2) The plasma rennin activity and angiotensin II (AngII) level among the EH patients were (1.95 +/- 0.11) microgram .L(-1).h(-1) and (72.6 +/- 4.6) ng/L, all significantly higher than those in the controls [(1. 59 +/- 0.11) microgram .L(-1).h(-1) and (51.7 +/- 4.6) ng/L, all P < 0.05].(3) The -6G allele frequency in the promoter of AGT gene was higher in EH group than in the control group (0.36 vs 0.27, kappa(2) = 9.35, P < 0.01). There was a weak association between -6A -->G variant and the plasma AngII level, and there was no significant difference in the genotype distribution and allele frequency of M235T variant between the hypertensive and normotensive groups (P > 0.05). CONCLUSION: Genetic factor plays an important role in the pathogenesis of essential hypertension and angiotensinogen gene might be one of the most key susceptibility genes for essential hypertension in Tibetan.