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Biomedical subjects

Fang Zheng

Publications and source records attributed to Fang Zheng.

At least 37 records · Page 2Linked to original sources
PubMed2006

Practical application of fluorescent quantitative PCR on Trisomy 21 in Chinese Han population.

OBJECTIVE: To apply the fluorescent quantitative PCR method on the detection of Trisomy 21 by D21S11 locus and make a foundation for rapid prenatal diagnosis of Trisomy 21. METHODS: About 409 controls (39 amniotic fluid samples and 370 peripheral blood samples) and 35 patients (4 amniotic fluid samples and 31 peripheral blood samples) with Trisomy 21 were tested using fluorescent quantitative PCR by amplification of DNA fragment on D21S11 STR locus. The results were compared with conventional cytogenetic analysis to confirm the utility of this method. And the allele frequency distributions of D21S11 STR locus were analyzed. RESULTS: The 95% reference interval of fluorescent intensity ratios of peak heights of PCR products amplified from two alleles on D21S11 locus ranged from 0.84 to 1.42 (1.13 +/- 0.29) in heterozygous controls. About 19 out of 35 patients showed a "diallelic" pattern and their height ratio of fluorescent peaks of PCR products amplified from two alleles in patients with "diallelic" patterns were all outside of the 95% reference range of controls. The PCR products of DNA from 12 patients presented the third allele. No sample with the "monoallelic" pattern was found. Four chimeras diagnosed by cytogenetic method could not be diagnosed by this method. There were 17 and 11 alleles found in controls and patients, respectively. About 343 out of 409 controls were heterozygous and the heterozygosity was 83.86%. We did not find any significant differences in the frequency distributions of alleles on D21S11 locus between controls and patients. But there were significant differences in the frequency distributions of alleles on D21S11 locus between controls and patients. But there were significant differences in the frequency distributions of alleles on D21S11 locus among different populations. CONCLUSIONS: The fluorescent quantitative polymerase chain reaction method was rapid, accurate, and only small amount of starting material was needed, it could be applied in rapid prenatal diagnosis of Trisomy 21. D21S11 was a good marker with high heterozygosity for the screening of Trisomy 21. And the frequency distributions of alleles on D21S11 locus were significantly related to ethnic background.

Amniotic Fluid↗
PubMed2006

Association study between fibronectin and coronary heart disease.

Fibronectin is a known chemoattractant for several cell types that play a role in the wound healing process, including fibroblasts, endothelial cells and macrophages. It also generates a scaffold that allows attachment of other extracellular matrix components. Large amounts of fibronectin have been detected in atherosclerotic plaques, suggesting that it may play a role in the pathogenesis of atherosclerosis. To examine the possible involvement of fibronectin in the etiology of atherosclerotic coronary heart disease, we analyzed four polymorphisms in the human fibronectin gene and determined the plasma fibronectin levels in patients with coronary heart disease (n = 109) and age- and gender-matched controls (n = 123) in Chinese Han people. No significant positive association was observed between these polymorphisms and coronary heart disease. The levels of circulating plasma fibronectin, however, were significantly lower in patients with coronary heart disease (mean +/- SD 245 +/- 87 mg/L) compared with controls (354 +/- 88 mg/L) (p < 0.001). The odds ratio (OR) for plasma fibronectin was 0.94 in a multivariate unconditional logistic regression model (OR = 0.94, 95% CI 0.91-0.96, p < 0.001). We conclude that, in our population, the four fibronectin gene polymorphisms detected are not associated with clinical coronary heart disease. Our data suggest that low circulating fibronectin levels might be a new marker of coronary heart disease.

Alleles↗
PubMed2006

Soluble mouse B7-H3 down-regulates dendritic cell stimulatory capacity to allogenic T cell proliferation and production of IL-2 and IFN-gamma.

B7-H3 is a recently identified member of the B7 gene family. Its ubiquitous expression in both lymphoid and nonlymphoid tissues suggests that it could play an important role in the maintenance of self-tolerance. However, the exact function of B7-H3 is still elusive. The purpose of current study is to demonstrate the possible function of soluble mouse B7-H3 for prevention of DC-mediated T cell activation. For this purpose, we established a soluble mouse B7-H3 fusion protein (mB7h3-hIg) eukaryotic expression vector (pmB7h3-hIg) with a C-terminal human IgG1 Fc. A C57BL/6 (B6)-derived dendritic cell line (DC2.4 cells) was used for the establishment of stable transfectants for generation of soluble mB7h3-hIg. Ectopic mB7h3-hIg expression was confirmed by RT-PCR, Western blot and ELISA analyses. A 49.7 kD protein was detected by Western blot from DC2.4 cells transfected with pmB7h3-hIg. It was found that soluble mB7h3-hIg expression has no effect on cell cycling and apoptosis and the expression of CD80 and CD86 of the DC2.4 cells. However, ectopic soluble mB7h3-hIg expression was found to significantly affect the allo-stimulatory capability for DC2.4 cells. DC2.4 cells expressing soluble mB7h3-hIg showed a significant reduced allo-stimulatory capability as compared with the controls determined by MLC. Further studies revealed that soluble mB7h3-hIg could also inhibit IL-2 and IFN-gamma production of allogenic T cells. These results suggested a great potential of soluble B7-H3 for treatment of graft rejection and autoimmume disease.

Animals↗
PubMed2005

Modeling multiple species of nicotine and deschloroepibatidine interacting with alpha4beta2 nicotinic acetylcholine receptor: from microscopic binding to phenomenological binding affinity.

A variety of molecular modeling, molecular docking, and first-principles electronic structure calculations were performed to study how the alpha4beta2 nicotinic acetylcholine receptor (nAChR) binds with different species of two typical agonists, (S)-(-)-nicotine and (R)-(-)-deschloroepibatidine, each of which is distinguished by different free bases and protonation states. On the basis of these results, predictions were made regarding the corresponding microscopic binding free energies. Hydrogen-bonding and cation-pi interactions between the receptor and the respective ligands were found to be the dominant factors differentiating the binding strengths of different microscopic binding species. The calculated results and analyses demonstrate that, for each agonist, all the species are interchangeable and can quickly achieve a thermodynamic equilibrium in solution and at the nAChR binding site. This allows quantitation of the equilibrium concentration distributions of the free ligand species and the corresponding microscopic ligand-receptor binding species, their pH dependence, and their contributions to the phenomenological binding affinity. The predicted equilibrium concentration distributions, pK(a) values, absolute phenomenological binding affinities, and their pH dependence are all in good agreement with available experimental data, suggesting that the computational strategy from the microscopic binding species and affinities to the phenomenological binding affinity is reliable for studying alpha4beta2 nAChR-ligand binding. This should provide valuable information for future rational design of drugs targeting nAChRs. The general strategy of the "from-microscopic-to-phenomenological" approach for studying interactions of alpha4beta2 nAChRs with (S)-(-)-nicotine and (R)-(-)-deschloroepibatidine may also be useful in studying other types of ligand-protein interactions involving multiple molecular species of a ligand and in associated rational drug design.

Binding Sites↗
PubMed2005

Detecting the polymorphisms of paraoxonase (PON) cluster in Chinese Han population based on a rapid method.

BACKGROUND: An increased risk of coronary heart disease has been shown to be associated with polymorphisms in PON1 gene in different populations. Polymorphisms in PON2 gene have been associated with the level of plasma lipoproteins and glucose and are thought to play a role in atherosclerosis. METHODS: To detect PONs polymorphisms more rapidly and reliably, we modified and improved the method established by Motti et al. We redesigned the primer for amplifying the common polymorphism at position 311 of PON2, which produced more reliable and efficient amplification. RESULTS: A second common polymorphism at codon 148 was also detected by our new method, as were the 2 polymorphisms in the PON1 gene. The new method allowed identification of 4 polymorphisms (PON1-192, PON1-55, PON2-148 and PON2-311) simultaneously. The PONs genotypes of 82 healthy persons were identified by this method. The allelic frequencies were: PON1-192: Q 46.3%, R 53.7%; PON1-55: L 95.1%, M 4.9%; PON2-148: A 85.4%, G 14.6%; PON2-311: S 77.4%, and C 22.6%, respectively. CONCLUSION: This method represents a simple, economical and time-saving technique to simultaneously detect 4 polymorphisms in the PON cluster. It provides a useful application to enable further study of the relationship between PON1 and PON2 and their role in atherosclerosis.

Aged↗
PubMed2005

Polymorphisms of estrogen-metabolizing genes and breast cancer risk: a multigenic study.

BACKGROUND: Endogenous estrogen plays a very important role in the carcinogenesis and progression of breast cancer. The enzymes involved in the biosynthesis and metabolism of estrogen have been proposed to contribute to this effect. To examine this hypothesis, we conducted a case-control study to investigate the relationship between polymorphisms of genes responsible for estrogen biosynthesis (CYP17, cytochrome P450c17a and CYP19, aromatase cytochrome P450) and estrogen sulfation of inactivation (SULT1A1, sulfotransferase1A1) and the risk of breast cancer in Chinese women. METHODS: This study involved 213 breast cancer patients and 430 matched controls. PCR-based restriction fragment length polymorphism (RFLP) and short tandem repeat polymorphism (STRP) assays were used to detect the mononucleotide transition of CYP17 and SULT1A1 and tandem repeat polymorphism of CYP19. Logistic regression analyses were used to determine OR and 95% CI of each and all three high-risk genotypes, of all three genotypes combined, and of estrogen exposure factors. The relationship between each high-risk genotype and clinicalpathological characteristics were also assessed. RESULTS: The frequency of A2 allele of CYP17 was 49.8% in cases and 49.1% in controls (P = 0.82). The frequency of His allele of SULT1A1 was significantly higher in cases (13.6%) than in controls (9.5%) (P < 0.05). There was also significant difference of the (TTTA) 10 allele of CYP19 which was 12.4% in cases and 8.2% in controls (P < 0.05). When the CYP17 A2 allele, CYP19 (TTTA) 10 and SULT1A1 His allele were considered as the "putative high-risk" genotype, there was an increased risk of breast cancer with the number of high-risk genotypes in a dose-response effect (trend, P = 0.05). In multivariate analysis, the SULT1A1 genotype remained the most significant determinant for breast cancer, with OR = 2.37 (95% CI 1.23-4.74), followed by CYP19, with OR = 1.75 (95% CI 1.27-3.56). The (TTTA) 10 allele of CYP19 was associated with tumor size, and the His allele of SULT1A1 associated with status of lymph node metastasis. CONCLUSIONS: This study supports the hypothesis that breast cancer can be initiated by estrogen exposure and that estrogen metabolizing genes are involved in this mechanism. This multigenic model is useful for identifying individuals who are at higher risks of breast cancer.

Adult↗
PubMed2005

Molecular determinants of glycine-independent desensitization of NR1/NR2A receptors.

Glycine-independent desensitization is thought to be an important regulatory mechanism for the function of N-methyl-D-aspartate (NMDA) receptors. Previous studies have suggested that the molecular determinants for glycine-independent desensitization are located at two distinct domains of NR2A, i.e., the amino-terminal domain (ATD) and the pre-M1 domain. Since the glycine-independent desensitization described in these earlier studies was a mixture of glycine-independent desensitization and zinc-dependent apparent desensitization, the exact role of these two domains in glycine-independent desensitization remains in question. In the present study, we show that deletion of the ATD of NR2A or mutating the pre-M1 region of NR2A causes no detectable changes in the degree or the time constant of glycine-independent desensitization. Therefore, the ATD and the pre-M1 domain of NR2A play no significant role in glycine-independent desensitization of NR1/NR2A receptors. On the other hand, several residues in the lurcher motif of either NR1 or NR2A are critical for the glycine-independent desensitization of NR1/NR2A receptors. In addition to NR1a(A653T) and NR2A(A651T), NR1a(T648C), NR1a(A649C), NR2A(T646C), and NR2A(A647C) show significantly reduced glycine-independent desensitization. Since all these mutations also alter the proton sensitivity or deactivation time constants of NR1/NR2A receptors, our data suggest that the channel gating and desensitization of NMDA receptors share common molecular determinants and that the lurcher motif of NR1 and NR2A is critical for both processes.

Binding Sites↗
PubMed2005

Improved surgical outcome by modification of porcine dermal collagen implant in abdominal wall reconstruction in rats.

AIM: We earlier showed in rats that fascial repair with Pelvicol, a porcine dermal collagen implant, was associated with a lesser inflammatory response but lower tensile strength in the early postoperative period as compared to Prolene. Herein we wanted to evaluate whether creation of pores in Pelvicol, facilitating ingrowth of fibrous tissue and vessels, would result in a higher tensile strength at d30 without compromising longer term results. METHODS: First tensile strength of Pelvicol modified with different pore sizes was evaluated ex vivo. In a second step, Pelvicol implants with pores were used to cover full-thickness abdominal wall defects in 36 rats. Implants were either Pelvicol (non-porous) or with pores of Phi : 0.7, 1.2, or 2.0 mm (n=6 each). Animals were sacrificed on d30 and 90 to evaluate the presence of herniation, infection, adhesions, change in thickness and tensile strength. Histopathology was performed to assess inflammatory response and collagen deposition. Data were compared to available data on Prolene implanted animals at same time points. RESULTS: Pelvicol with pore diameter of 2.5 mm was significantly weaker ex vivo. Animals repaired with non-porous material did develop seroma (2/6) or clinical infection (1/6) whereas none in the other groups did. There was a trend for increasing tensile strength at 30 d with increasing pore diameter, being significant in the 2.0-mm pore size group. This difference disappeared by 90 d, where all materials were equally strong as Prolene. The foreign body reaction was less intense in a pore-size dependent manner, with more abundant neo-vascularization and collagen deposition passing through the pores. CONCLUSION: Creation of pores in Pelvicol promotes neo-vascularization, collagen deposition, and fibrous tissue ingrowth, and at pore size 2.0 mm tensile strength was increased at d30 whereafter all materials had comparable strength.

Abdominal Wall↗
PubMed2005

Comparison of host response to polypropylene and non-cross-linked porcine small intestine serosal-derived collagen implants in a rat model.

OBJECTIVE: To compare the host response, architectural integration and tensile strength of polypropylene and porcine small intestine submucosa-derived implants in a rat model. DESIGN: Experimental study. SETTING: Center for Surgical Technologies, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium. SAMPLE: Forty-eight adult male Wistar rats weighing 220-250 g randomised to receive either implant. METHODS: Full thickness abdominal wall defects were primarily repaired with polypropylene mesh (Marlex) (MX group) or porcine small intestine submucosa (Surgisis) (SIS group). Animals were sacrificed at 7, 14, 30 and 90 days after implantation. MAIN OUTCOME MEASURES: The presence of herniation, infection and intra-peritoneal adhesions. Change in thickness and tensile strength of implant. Histopathological and immunohistochemical appearances of inflammatory response and collagen deposition. RESULTS: Implants from the SIS group showed a short term increase in thickness in the first 14 days. Formation of adhesions was significantly more intense in the MX group at 30 days, and more extensive in the SIS group at 90 days. Tensile strength increased over time in both groups but was significantly lower in the SIS group than the MX group at 30 days. Implants in the MX group showed a more pronounced inflammatory response and more pronounced new vessel formation than the SIS group. Collagen formation was initially more fibrous and better organised in the MX group but became greater in the SIS group at 90 days. CONCLUSIONS: Biologically derived implant material induced a less pronounced inflammatory response and differences in collagen deposition. At 30 days tensile strength was weaker in the biological implant group but was equivalent by 90 days. These differences may have implications for the in vivo performance of the materials.

Abdominal Wall↗
PubMed2005

[The apolipoprotein E-CI-CII gene cluster polymorphisms and coronary artery disease].

OBJECTIVE: To investigate associations between the apolipoprotein E-CI-CII gene cluster polymorphisms and coronary artery disease (CAD). METHODS: apoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the polymorphisms of both apoCI and apoCII genes were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 203 cases of CAD and 365 controls. Pairwise linkage disequilibrium coefficients (D, D') were estimated by the LINKAGE program. RESULTS: The frequencies of apoE E3/4 genotype (0.259) and epsilon4 (0.139) in CAD group were significantly higher than that in control group (0.125, 0.069), (P<0.05). The significant difference was also found for the apoCI locus, the frequencies of H2 allele were 0. 205 in the CAD and 0.113 in the control. Linkage disequilibrium coefficient D' was 0.672 (P<0.01) between apoE and apoCI genes. Significant differences for a deficit of epsilon3-H1-T1 and excess of epsilon4-H2-T1 were found in the CAD by estimation of the haplotype frequencies. After adjustment for possible confounding factors, the multivariate Logistic analysis showed a significant interaction among epsilon4, H2 and smoking, OR value was 18.3 (95%CI:2.35-150.81, P<0.05), attributable proportions of interaction (API) was 57.3%, it was a multiplicative model. An additive model was shown among epsilon4, H2 and bibulosity; the odds ratio (OR) (95%CI) and API of their interaction were 12.7(2.8-58.6, P<0.05) and 43.5%, respectively. CONCLUSION: The results suggested that both apoE and apoCI on chromosome 19 were the susceptibility loci for CAD, their linkage disequilibrium should be responsible for the development of CAD. Smoking and bibulosity can significantly increase the risk of CAD.

Aged↗
PubMed2005

[Apolipoproptein E-CI-CII gene cluster and its effect on serum lipid levels].

OBJECTIVE: To investigate the allele frequencies of the apolipoprotein (apo)E-CI-CII cluster gene in Hans of Chinese, and its relation to serum lipid levels. METHODS: The study subjects consisted of healthy individuals (male: 196, female: 154; average age: 63.6 +/- 12.0 years) who were randomly selected from health screening. ApoE genotypes were identified by multi-AMRS PCR and both the ApoCI promoter polymorphisms and AvaII polymorphisms of the apoCII gene were detected by using PCR-RFLP. The serum lipid levels were determined using an automatic chemistry analyzer. RESULTS: For ApoE gene, the frequency of E3/3 was 73.4%, it represents the most common genotype from of the polymorphism. The frequencies of E2/2, E2/4 and E4/4 genotypes were all smaller than 1%. For the ApoCI locus, the frequencies of H1/ 1, H2/2 genotypes were 79.7% and 1.7%, respectively. Both the ApoE and ApoCI polymorphisms showed the lack of association with plasma levels in this population. The linkage disequilibrium between ApoE with ApoCI wasn't found, either. The allele frequencies of ApoCII gene were T1 : 70.7% and T2 : 29.3%, respectively. The TG level in subjects carrying with T1/2 (1.49 +/- 0.96 mmol/l) was significant higher than that in subjects with T1/1 (1.29 +/- 0.72 mmol/l), P < 0.05. No significant differences were found between male and female in genotype distribution and allele frequencies of the ApoE-CI-CII gene cluster. CONCLUSION: This result suggested that it might be one of the factors in explaining the lower prevalence rate of atherosclerosis in the China population.

Adult↗
PubMed2005

[Association of mitochondrial DNA variation with type 2 diabetes mellitus].

OBJECTIVE: To explore the prevalence of mitochondrial DNA (mtDNA) mutations in patients with type 2 diabetes mellitus in Hubei. METHODS: A total of 184 cases of type 2 diabetes mellitus and 210 matched healthy controls with normal glucose tolerance were recruited for the study. The variants of mtDNA, including MIND13316 (G-->A), MIND13394 (T-->C), MTTE14693 (A-->G), MTTL1 3243 (A-->G), MTRNA1310 (C-->T) and 16189 (T-->C), were screened using PCR-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing. The mutations were analyzed by mfold or tRNAscan-SE softwares. RESULTS: The mutation rates of 3316 (G-->A), 3394 (T-->C), 14693 (A-->G) were 3.26%, 2.72% and 2.17% respectively in type 2 diabetes group, whereas in the control group, the point mutations of 3394 (T-->C) and 14693 (A-->G) were not detected, but two subjects with 3316 (G-->A) were found (0.99%). There were significant differences in mutation rates of 3394 (T-->C) and 14693 (A-->G) between the two groups (P<0.05). In 4 of 184 cases, a T to C transition at nucleotide position 14693 was uncovered for the first time. The prevalence of 16189 variant among type 2 diabetes was significantly higher that of the controls (36.9% vs 26.6%, P=0.03). Moreover, the type 2 diabetes with 16189 variant showed higher fasting serum insulin level and higher HOMA-IR level than those without 16189 variant; stepwise multiple regression analysis showed the 16189 variant was an independent factor contributing to HOMA-IR (R(2)=0.043, P=0.037). Secondary structure prediction revealed that there were differences in 3394 T-->C vs wild-type ND1 protein and in 14693 A-->G vs wild-type tRNA(Glu) protein. CONCLUSION: The mutations of 3394 (T-->C) and 14693 (A-->G) may contribute to the genetic predisposition to type 2 diabetes; 16189 (T-->C) variant is associated with insulin resistance and risk factor of diabetes.

Aged↗
PubMed2004

M2 muscarinic acetylcholine receptor knock-out mice show deficits in behavioral flexibility, working memory, and hippocampal plasticity.

Muscarinic acetylcholine receptors are known to play key roles in facilitating cognitive processes. However, the specific roles of the individual muscarinic receptor subtypes (M1-M5) in learning and memory are not well understood at present. In the present study, we used wild-type (M2+/+) and M2 receptor-deficient (M2-/-) mice to examine the potential role of M2 receptors in learning and memory and hippocampal synaptic plasticity. M2-/- mice showed significant deficits in behavioral flexibility and working memory in the Barnes circular maze and the T-maze delayed alternation tests, respectively. The behavioral deficits of M2-/- mice were associated with profound changes in neuronal plasticity studied at the Schaffer-CA1 synapse of hippocampal slices. Strikingly, short-term potentiation (STP) was abolished, and long-term potentiation (LTP) was drastically reduced after high-frequency stimulation of M2-/- hippocampi. Treatment of M2-/- hippocampal slices with the GABA(A) receptor antagonist, bicuculline, restored STP and significantly increased LTP. Whole-cell recordings from CA1 pyramidal cells demonstrated a much stronger disinhibition of GABAergic than glutamatergic transmission in M2-/- hippocampi, which was particularly prominent during stimulus trains. Increased strength of GABAergic inhibition is thus a likely mechanism underlying the impaired synaptic plasticity observed with M2-/- hippocampi. Moreover, the persistent enhancement of excitatory synaptic transmission in CA1 pyramidal cells induced by the transient application of a low concentration of a muscarinic agonist (referred to as LTP(m)) was totally abolished in M2-/- mice. Because impaired muscarinic cholinergic neurotransmission is associated with Alzheimer's disease and normal aging processes, these findings should be of considerable therapeutic relevance.

Amnesia↗
PubMed2004

Differential effects on current kinetics by point mutations in the lurcher motif of NR1/NR2A receptors.

The extracellular proton site has emerged as the key site in regulating N-methyl-d-aspartate (NMDA) receptor function. However, the molecular determinants for the proton-sensitive gating of NMDA receptors are still not clearly delineated. The highly conserved lurcher motif plays an important role in determining the proton sensitivity of NMDA receptors. Mutations of several residues in the lurcher motif of either NR1 or NR2A significantly reduce proton sensitivity of recombinant NR1/NR2A receptors. It remains uncertain how these residues play a role in proton inhibition of NMDA receptors. Mutations of these residues could directly reduce the proton affinity. Alternatively, they could alter the proton IC(50) indirectly by increasing channel open probability. In the present study, we recorded the macroscopic NMDA currents in HEK 293 cells with a piezo-based rapid solution exchange system. We show that zinc slows the deactivation of NR1a(A653T)/NR2A receptors and NR1a/NR2A(A651T) receptors. However, NR1a(T648C)/NR2A, NR1a/NR2A(T646C), NR1a(A649C)/NR2A, NR1a/NR2A(A647C), and NR1a(A653T)/NR2A exhibit significantly slower rise time and deactivation time constants under nominally zinc-free conditions. Our data suggest that the channel open probability for these mutant receptors may be significantly increased. The reduction in proton sensitivity by these mutations could be accounted for, at least partially, by the increased channel open probability. In contrast, NR1a/NR2A(A651T) exhibits normal macroscopic currents, suggesting that the reduction of proton sensitivity by this mutation cannot be attributed to any significant change of open probability. Further experiments are needed to determine the exact role of this residue in proton-sensitive gating of NMDA receptors.

Amino Acid Motifs↗
PubMed2004

Sulfotransferase 1A1 (SULT1A1) polymorphism and breast cancer risk in Chinese women.

BACKGROUND: Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, catalyzes the sulfation of a variety of phenolic and estrogenic compounds. A functional polymorphism of the SULT1A1 gene has been implicated in a decreased activity and thermostability when the wild-type arginine (Arg) at codon 213 is substituted by a histidine (His). METHODS: We investigated the association between the His allele and the risk breast cancer in 213 cases and 430 matched controls in Chinese women, and the interaction between His allele and endogenous estrogen and dietary mutagens exposure factors were also determined by use of logistic regression analysis. RESULTS: There was no significant difference in genotypes between the cancer patients and control populations. However, the frequency of the His allele in cases (13.6%) were significant higher than that in controls (9.5%), P = 0.03. Compared with women carrying the Arg/Arg genotype, the adjusted odds ratio (OR) of Arg/His was 1.48 (95% CI = 0.59-3.31) and His/His was 2.28 (95% CI = 0.69-9.58), P trend was 0.04. The adjusted OR of Arg/His + His/His was 2.60 (95% CI = 1.12-6.05). His allele strengthen the effect of endogenous estrogen exposure with interaction index r > 1, and weaken the effect of heterocyclic amines and polycyclic aromatic hydrocarbons derived from dietary with interaction index r > 1, both were multiplicative interaction model. CONCLUSIONS: Our findings suggest that the SULT1A1 His allele was positively associated with the risk of breast cancer in Chinese women. And there was interaction between SULT1A1 polymorphism and related exposure factors.

Adult↗
PubMed2004

[Interaction of ApoE and LDL-R gene polymorphisms and alcohol drinking and smoking on coronary heart disease].

OBJECTIVE: To investigate the association between the ApoE and LDLR-R gene loci on coronary heart disease (CHD) and their interaction with alcohol drinking and smoking in Hans of Chinese. METHODS: A questionnaire survey of the behaviors of smoking and drinking, dietary custom, and anamnesis, was conducted among 146 cases of CHD, aged 64 +/- 11, and 340 controls, aged 63 +/- 12. Peripheral blood samples were collected and the total DNAs were extracted. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were examined. The ApoE genotype was identified by the method of multiplex amplification refractory mutation system and AvaII polymorphisms of the LDL-R gene were detected by using the method of polymerase chain reaction-restriction fragment length polymorphism. The interaction between the genes and alcohol drinking and smoking was analyzed by using multivariate logistic regression models. RESULTS: (1) Both the systolic blood pressure and diastolic blood pressure of the CHD patients (132 mm Hg +/- 21 mm Hg, and 81 mm Hg +/- 13 mm Hg, 1 mm Hg = 0.133 kPa) were significantly higher than those of the controls (123 mm Hg +/- 17 mm Hg and 77 mm Hg +/- 11 mm Hg, both P < 0.05). The level of TG was 1.6 +/- 0.9 mmol/L in the CHD group, significantly higher than that in the control group (1.4 +/- 0.8 mmol/L, P < 0.05). However, there was no difference in the levels of TC, LDL-C, and HDL-C between the 2 groups (all P > 0.05). (2) For the ApoE gene, the frequencies of E4/3 genotype and epsilon 4 allele were 24.0% and 13.4% respectively in the CHD group, both significantly higher than those in the control group (12.9% and 7.2% respectively, both P < 0.05). For the LDLR-AvaII locus, no difference was found in different genotypes between the CHD and control groups. However, the proportion of those with epsilon 4 locus and AvaII(+) locus simultaneously was 60% in the CHD group, significantly higher than in the control group (31.8%, P < 0.05). (3) After adjustment of confounding variables, such as age, sex, blood pressure, and body mass index, the binary logistic analysis showed a significant gene-environment interaction (P < 0.05). The OR value were: for epsilon 4-AvaII(+): 2.99 (95% CI: 1.36 approximately 6.66, P < 0.01), for epsilon 3-often drinking: 2.60 (95% CI: 1.35 approximately 5.02, P < 0.01), for epsilon 3-smoking 2.58 (95% CI: 1.16 approximately 5.71, P < 0.05), for epsilon 4-stopped smoking 3.12 (95% CI: 1.23 approximately 8.09, P < 0.05), for epsilon 4-smoking: 5.30 (95% CI: 1.21 approximately 23.22, P < 0.05), and for AvaII(+)-often drinking: 2.49 (95% CI: 1.12 approximately 5.52, P < 0.05) respectively. CONCLUSION: The carriers of epsilon 3, epsilon 4 or AvaII(+) alleles would have higher risk of suffering from CHD if they are drink alcohol or smoke heavily.

Adult↗
PubMed2004

Studies on activity of NK cells in preeclampsia patients.

The activity of the NK cells in patients with preeclampsia was studied to investigate the pathogenesis of preeclampsia. By using MTT and 51Cr releasing technique, the proliferation and killing ability of the NK cells in maternal and umbilical blood from preeclampsia patients (n = 18) and normal third trimester pregnant women (n = 18) were detected. The NK-92 cell line was as the positive control. The results showed that the NK cell counts of umbilical blood in preeclampsia patients and normal third trimester pregnant women were significantly greater than those of maternal blood (both P<0.05). Compared with that in normal third trimester pregnant women, the proliferative ability of the NK cells in preeclampsia patients was apparently increased (P<0.05). Compared with that in maternal blood, the proliferative ability of the NK cells in umbilical blood from both preeclampsia patients and normal third trimester pregnant women was dramatically increased. The killing ability of the NK cells in preeclampsia patients was significantly higher than that in normal third trimester pregnant women (P <0.05). It was suggested that both number and function of the NK cells in preeclampsia women were increased, and that in umbilical blood was greater than that in maternal blood, speculating that the function of the NK cells may affect the maintenance of the maternal and fetal immune tolerance during pregnancy.

Adult↗