Long-term complete response to anti-programmed-death-1 monotherapy in a patient with relapsed and refractory ovarian adenocarcinoma: A case report.

BACKGROUND: Ovarian cancer is the most common malignant tumor of the female reproductive system, and the survival rate of patients with relapsed and refractory ovarian cancer is very low. CASE SUMMARY: Here, we report a case of high-grade serous papillary adenocarcinoma of the ovary that was successfully treated with immunotherapy. Radical surgery and adjuvant chemotherapy for the 56-year-old patient were successful; however, her tumor relapsed. Subsequent second-line chemotherapy, targeted agents, and other treatments were ineffective, as the tumor continued to recur and metastasize. Anti-programmed cell death-1 (PD-1) monotherapy (tislelizumab) completely alleviated the tumor, and the multiple metastatic tumors disappeared. To date, the patient has used anti-PD-1 for 32 months, experiencing no disease progression and maintaining good health without additional treatment. CONCLUSION: This case suggests that anti-PD-1 immunotherapy may have long-term positive effects on outcomes in some refractory recurrent solid tumors. Further research is needed to identify patients most likely to respond to anti-PD-1 therapy.

Early-life perfluorooctanoic acid exposure disrupts the function of dopamine transporter protein with glycosylation changes implicating the links between decreased dopamine levels and disruptive behaviors in larval zebrafish.

Exposure to perfluorooctanoic acid (PFOA) during early embryonic development is associated with the increased risk of developmental neurotoxicity and neurobehavioral disorders in children. In our previous study, we demonstrated that exposure to PFOA affected locomotor activity and disrupted dopamine-related gene expression in zebrafish larvae. Consequently, we continue to study the dopaminergic system with a focus on dopamine levels and dopamine's effect on behaviors in relation to PFOA exposure. In the present study, we found a decrease in dopamine levels in larval zebrafish. We studied the dopamine transporter (DAT) protein, which is responsible for regulating dopamine levels through the reuptake of dopamine in neuronal cells. We demonstrated that exposure to PFOA disrupted the glycosylation process of DAT, inhibited its uptake function, and induced endoplasmic reticulum (ER) stress in dopaminergic cells. Besides, we conducted a light-dark preference test on larval zebrafish and observed anxiety/depressive-like behavioral changes following exposure to PFOA. Dopamine is one of the most prominent neurotransmitters that significantly influences human behavior, with low dopamine levels being associated with impairments such as anxiety and depression. The anxiety-like response in zebrafish larvae exposure to PFOA implies the link with the reduced dopamine levels. Taken together, we can deduce that glycosylation changes in DAT lead to dysfunction of DAT to regulate dopamine levels, which in turn alters behavior in larval zebrafish. Therefore, alternation in dopamine levels may play a pivotal role in the development of anxiety/depressive-like behavioral changes induced by PFOA.

Perfluorooctanoic acid disrupts thyroid-specific genes expression and regulation via the TSH-TSHR signaling pathway in thyroid cells.

Perfluorooctanoic acid (PFOA) is a highly persistent and widespread chemical in the environment with endocrine disruption effects. Although it has been reported that PFOA can affect multiple aspects of thyroid function, the exact mechanism by which it reduces thyroxine levels has not yet been elucidated. In this study, FRTL-5 rat thyroid follicular cells were used as a model to study the toxicity of PFOA to the genes related to thyroid hormone synthesis and their regulatory network. Our results reveal that PFOA interfered with the phosphorylation of the cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) induced by thyroid-stimulating hormone (TSH), as well as the transcription levels of paired box 8 (PAX8), thyroid transcription factor 1 (TTF1), sodium/iodide cotransporter (NIS), thyroglobulin (TG), and thyroid peroxidase (TPO). However, the above outcomes can be alleviated by enhancing cAMP production with forskolin treatment. Further investigations showed that PFOA reduced the mRNA level of TSH receptor (TSHR) and impaired its N-glycosylation, suggesting that PFOA has disrupting effects on both transcriptional regulation and post-translational regulation. In addition, PFOA increased endoplasmic reticulum (ER) stress and decreased ER mass in FRTL-5 cells. Based on these findings, it can be inferred that PFOA disrupts the TSH-activated cAMP signaling pathway by inhibiting TSHR expression and its N-glycosylation. We propose that this mechanism may contribute to the decrease in thyroid hormone levels caused by PFOA. Our study sheds light on the molecular mechanism by which PFOA can disrupt thyroid function and provides new insights and potential targets for interventions to counteract the disruptive effects of PFOA.

Genome-wide placental DNA methylations in fetal overgrowth and associations with leptin, adiponectin and fetal growth factors.

BACKGROUND: Fetal overgrowth "programs" an elevated risk of type 2 diabetes in adulthood. Epigenetic alterations may be a mechanism in programming the vulnerability. We sought to characterize genome-wide alterations in placental gene methylations in fetal overgrowth and the associations with metabolic health biomarkers including leptin, adiponectin and fetal growth factors. RESULTS: Comparing genome-wide placental gene DNA methylations in large-for-gestational-age (LGA, an indicator of fetal overgrowth, n = 30) versus optimal-for-gestational-age (OGA, control, n = 30) infants using the Illumina Infinium Human Methylation-EPIC BeadChip, we identified 543 differential methylation positions (DMPs; 397 hypermethylated, 146 hypomethylated) at false discovery rate < 5% and absolute methylation difference > 0.05 after adjusting for placental cell-type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. Twenty-five DMPs annotated to 20 genes (QSOX1, FCHSD2, LOC101928162, ADGRB3, GCNT1, TAP1, MYO16, NAV1, ATP8A2, LBXCOR1, EN2, INCA1, CAMTA2, SORCS2, SLC4A4, RPA3, UMAD1,USP53, OR2L13 and NR3C2) could explain 80% of the birth weight variations. Pathway analyses did not detect any statistically significant pathways after correcting for multiple tests. We validated a newly discovered differentially (hyper-)methylated gene-visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (LGA 47, OGA 47). Our data confirmed a hypermethylated gene-cadherin 13 (CDH13) reported in a previous epigenome-wide association study. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while leptin and fetal growth factors (insulin, IGF-1, IGF-2) were not. CONCLUSIONS: Fetal overgrowth may be associated with a large number of altered placental gene methylations. Placental VSX1 and CDH13 genes are hypermethylated in fetal overgrowth. Placental ADIPOQ gene methylations and fetal circulating adiponectin levels were correlated, suggesting the contribution of placenta-originated adiponectin to cord blood adiponectin.

Perfluorooctanoic acid exposure increases both proliferation and apoptosis of human placental trophoblast cells mediated by ER stress-induced ROS or UPR pathways.

Perfluorooctanoate acid (PFOA) is a highly persistent and widespread chemical in the environment. PFOA serum levels in pregnant women are positively associated with an increased risk of placenta-related disorders. However, the mechanism of PFOA cytotoxicity involved in placental cells and cellular responses such as ER stress remains poorly understood. In this study, we studied the cellular toxicity of PFOA with a focus on proliferation and apoptosis in a human placental trophoblast cell line. Cell viability, number, apoptosis, stress response, activation of the involved signaling pathways were assessed. Our results showed PFOA affected cell viability, proliferation and also resulted in apoptosis. Besides, both pro-proliferation and pro-apoptosis effects were attenuated by endoplasmic reticulum (ER) stress inhibitors. Further experiments demonstrated that two different signaling pathways were activated by PFOA-induced ER stress and involved in PFOA toxicity: the reactive oxygen species (ROS)-dependent ERK signaling triggered trophoblast proliferation, while the ATF4-dependent C/EBP homologous protein (CHOP) signaling was the trigger of apoptosis. We conclude that PFOA-induced ER stress is the trigger of proliferation and apoptosis of trophoblast via ROS or UPR signaling pathway, which leads to the altered balance critical to the normal development and function of the placenta.

Long-term use of ultra-low-dose mifepristone for uterine leiomyoma control and safety discussion: A case report.

RATIONALE: In recent years, many clinical trials have used low-dose mifepristone to control uterine fibroids, some of which have achieved good results. However, according to the classic concept, long-term use of mifepristone could induce malignant transformation of the endometrium, and the effect of ultra-low-dose of mifepristone on uterine fibroids is still uncertain. Researchers are short on cases of uterine fibroids treated with mifepristone for long periods (more than a year). PATIENT CONCERNS: A 47-year-old woman went to the hospital because of anemia. DIAGNOSES: The patient was diagnosed with uterine leiomyoma. INTERVENTIONS: The patient refused the suggestion of surgery, she was continuously treated with an ultra-low-dose (12.5 mg per 5 days) of mifepristone monotherapy for 4 years. OUTCOMES: The uterine leiomyoma was stable, anemia and other symptoms disappeared, and the menstrual cycle, liver and kidney function, and tumor markers were normal. LESSONS: Judging from our case, long-term, ultra-low-dose mifepristone for uterine fibroids treatment was safe and more effective than conventional therapy.

Behavioral effects of early-life exposure to perfluorooctanoic acid might synthetically link to multiple aspects of dopaminergic neuron development and dopamine functions in zebrafish larvae.

Perfluorooctanoic acid (PFOA) is known as an environmental endocrine disruptor and has developmental neurotoxicity that could be associated with behavior changes in human and animal studies. Previous studies have shown that PFOA might affect the dopaminergic nervous system. However, the mode of action underlying the effects of PFOA remains poorly understood. Our study used zebrafish as an animal model to investigate the effects of early-life PFOA exposure on dopaminergic neuron development and dopamine functions in zebrafish larvae. Zebrafish fertilized eggs were exposed to different concentrations of PFOA (0, 10, 100, 1000 µg/L). After exposure to PFOA for 7 days, the locomotor activity of zebrafish was decreased; the mRNA levels of nuclear receptor subfamily 4 group a member 2b (nr4a2b), paired box 2 and 5 (pax2, pax5), tyrosine hydroxylase 1/2 (th1/th2) and dopamine transporter (dat) were increased; mRNA and protein level of mesencephalic astrocyte-derived neurotrophic factor (manf) were decreased. Neural cell proliferation in the preoptic area of hypothalamus was increased. In conclusion, dopaminergic neuron development might be one of the targets of early-life PFOA exposure. The neurobehavior changes induced by PFOA exposure might link to multiple aspects of dopaminergic neuron development and dopamine functions in zebrafish larvae.

The triclosan-induced shift from aerobic to anaerobic metabolism link to increased steroidogenesis in human ovarian granulosa cells.

Triclosan (TCS) is an endocrine-disrupting chemical (EDC), which is used ubiquitously as an antimicrobial ingredient in healthcare products and causes contamination in the environment such as air, water, and biosolid-amended soil. Exposure to TCS may increase the risk of reproduction diseases and health issues. Several groups, including ours, have proved that TCS increased the biosynthesis of steroid hormones in different types of steroidogenic cells. However, the precise mechanism of toxic action of TCS on increased steroidogenesis at a molecular level remains to be elucidated. In this study, we try to address the mode of action that TCS affects energy metabolism with increased steroidogenesis. We evaluated the adverse effects of TCS on energy metabolism and steroidogenesis in human ovarian granulosa cells. The goal is to elucidate how increased steroidogenesis can occur with a shortage of adenosine triphosphate (ATP) whereas mitochondria-based energy metabolism is impaired. Our results demonstrated TCS increased estradiol and progesterone levels with upregulated steroidogenesis gene expression at concentrations ranging from 0 to 10 µM. Besides, glucose consumption, lactate level, and pyruvate kinase transcription were increased. Interestingly, the lactate level was attenuated with increased steroidogenesis, suggesting that pyruvate fate was shifted away from the formation of lactate towards steroidogenesis. Our study is gathering evidence suggesting a mode of action that TCS changes energy metabolism by predominating glucose flow towards the biosynthesis of steroid hormones. To the best of our knowledge, this is the first report that TCS presents such toxic action in disrupting hormone homeostasis.

Higher DNA Yield for Epidemiological Studies: A Better Method for DNA Extraction from Blood Clot.

BACKGROUND: Blood clots can be used to extract DNA, but they are not as widely used as whole blood or buffy coats. This is due not only because of the relatively low DNA yields and quality obtained from blood clots, but also because sampling prior to DNA extraction is more difficult. METHODS: To solve these problems, we compared several clot liquefaction methods, determined the four most feasible methods, and subsequently performed a comparative analysis among them. We compared the yields and optical density ratios of the resulting DNA samples and assessed their integrity using agarose gel electrophoresis, polymerase chain reaction, and next-generation sequencing (NGS). RESULTS: Each of the four methods has advantages and disadvantages. But in general, higher yields of DNA with better quality and integrity were obtained using the high-shear homogenization method than using the other three methods. Additionally, this method is cost-effective and feasible at large operational scales. The DNA yields and A260/280 ratios were optimal and stable, the operation time and labor costs were acceptable, and the success rate of NGS applications was 99.74%. Furthermore, we developed a simple and rapid method for cleaning the homogenizer head to remove residual samples. According to our experimental results, our cleaning method effectively eliminated the risk of cross-contamination caused by the homogenizer head. CONCLUSION: We recommend high-shear homogenization as a superior method for clot liquefaction. We believe that this method is worthy of large-scale application as it can improve the efficiency of DNA extraction from clots, thus reducing labor and economic costs.

Impact of Dehydroepiandrosterone Sulfate on Newborn Leukocyte Telomere Length.

The newborn setting of leukocyte telomere length (LTL) likely has important implications for telomere dynamics over the lifespan. However, its determinants are poorly understood. Hormones play an important role during pregnancy and delivery. We hypothesized that exposure to hormones may impact the fetal telomere biology system. To test this hypothesis, cortisol, estradiol, dehydroepiandrosterone sulfate (DHEAS) and reactive oxygen species (ROS) were measured in cord blood of 821 newborns from a prospective study. After accounting for the effects of potential determinants of newborn LTL, a 10-fold increase in DHEAS concentration was associated with a 0.021 increase in T/S ratio of newborn LTL (95% confidence interval: 0.009-0.034, P = 0.0008). For newborns who fell in the lowest quartile of DHEAS level, the mean newborn LTL was estimated to be approximately 2.0% shorter than the newborns in the highest DHEAS concentration quartile (P = 0.0014). However, no association was found between newborn LTL and cortisol or estradiol. As expected, newborns with higher ROS level (ROS > 260 mol/L) had lower LTL compared to that with lower ROS level (ROS ≤ 260 mol/L) (P = 0.007). There was also an inverse relationship between DHEAS and ROS (P < 1×10-4). Our findings suggest that exposure to DHEAS may exert a "programming" effect on the newborn telomere biology system.

Quality Analysis of DNA from Cord Blood Buffy Coat: The Best Neonatal DNA Source for Epidemiological Studies?

BACKGROUND: Umbilical cord blood is an economical and easy to obtain source of high-quality neonatal genomic DNA. However, although large numbers of cord blood samples have been collected, information on the yield and quality of the DNA extracted from cord blood is scarce. Moreover, considerable doubt still exists on the utility of the buffy coat instead of whole blood as a DNA source. METHODS: We compared the sample storage and DNA extraction costs for whole blood, buffy coat, and all-cell pellet. We evaluated three different DNA purification kits and selected the most suitable one to purify 1011 buffy coat samples. We determined the DNA yield and optical density (OD) ratios and analyzed 48 single-nucleotide polymorphisms using time-of-flight mass spectrometry (TOF MS). We also analyzed eight possible preanalytical variables that may correlate with DNA yield or quality. RESULTS: Buffy coat was the most economical and least labor-intensive source for sample storage and DNA extraction. The average yield of genomic DNA from 200 µL of buffy coat sample was 16.01 ± 8.00 µg, which is sufficient for analytic experiments. The mean A260/A280 ratio and the mean A260/A230 ratio were 1.89 ± 0.09 and 1.95 ± 0.66, respectively. More than 99.5% of DNA samples passed the TOF MS test. Only hemolysis showed a strong correlation with OD ratios of DNA, but not with yield. CONCLUSION: Our findings show that cord blood buffy coat yields high-quality DNA in sufficient quantities to meet the requirements of experiments. Buffy coat was also found to be the most economic, efficient, and stable source of genomic DNA.

Zbtb20 regulates the terminal differentiation of hypertrophic chondrocytes via repression of Sox9.

The terminal differentiation of hypertrophic chondrocytes is a tightly regulated process that plays a pivotal role in endochondral ossification. As a negative regulator, Sox9 is essentially downregulated in terminally differentiated hypertrophic chondrocytes. However, the underlying mechanism of Sox9 silencing is undefined. Here we show that the zinc finger protein Zbtb20 regulates the terminal differentiation of hypertrophic chondrocytes by repressing Sox9. In the developing skeleton of the mouse, Zbtb20 protein is highly expressed by hypertrophic chondrocytes from late embryonic stages. To determine its physiological role in endochondral ossification, we have generated chondrocyte-specific Zbtb20 knockout mice and demonstrate that disruption of Zbtb20 in chondrocytes results in delayed endochondral ossification and postnatal growth retardation. Zbtb20 deficiency caused a delay in cartilage vascularization and an expansion of the hypertrophic zone owing to reduced expression of Vegfa in the hypertrophic zone. Interestingly, Sox9, a direct suppressor of Vegfa expression, was ectopically upregulated at both mRNA and protein levels in the late Zbtb20-deficient hypertrophic zone. Furthermore, knockdown of Sox9 greatly increased Vegfa expression in Zbtb20-deficient hypertrophic chondrocytes. Our findings point to Zbtb20 as a crucial regulator governing the terminal differentiation of hypertrophic chondrocytes at least partially through repression of Sox9.

The zinc finger protein ZBTB20 regulates transcription of fructose-1,6-bisphosphatase 1 and ß cell function in mice.

BACKGROUND & AIMS: Fructose-1,6-bisphosphatase (FBP)-1 is a gluconeogenic enzyme that regulates glucose metabolism and insulin secretion in ß cells, but little is known about how its transcription is controlled. The zinc finger protein ZBTB20 regulates glucose homeostasis, so we investigated its effects on expression of FBP-1. METHODS: We analyzed gene expression using real-time reverse-transcription polymerase chain reaction, immunoblotting, and immunohistochemistry. We generated mice with ß cell-specific disruption of Zbtb20 using Cre/LoxP technology. Expression of Zbtb20 in ß cells was reduced using small interfering RNAs, and promoter occupancy and transcriptional regulation were analyzed by chromatin immunoprecipitation and reporter assays. RESULTS: ZBTB20 was expressed at high levels by ß cells and other endocrine cells in islets of normal mice; expression levels were reduced in islets from diabetic db/db mice. Mice with ß cell-specific knockout of Zbtb20 had normal development of ß cells but had hyperglycemia, hypoinsulinemia, glucose intolerance, and impaired glucose-stimulated insulin secretion. Islets isolated from these mice had impaired glucose metabolism, adenosine triphosphate production, and insulin secretion after glucose stimulation in vitro, although insulin secretion returned to normal levels in the presence of KCl. ZBTB20 knockdown with small interfering RNAs impaired glucose-stimulated insulin secretion in the ß cell line MIN6. Expression of Fbp1 was up-regulated in ß cells with ZBTB20 knockout or knockdown; impairments to glucose-stimulated insulin secretion were restored by inhibition of FBPase activity. ZBTB20 was recruited to the Fbp1 promoter and repressed its transcription in ß cells. CONCLUSIONS: The transcription factor ZBTB20 regulates ß cell function and glucose homeostasis in mice. It might be a therapeutic target for type 2 diabetes mellitus.

Fructose-1,6-bisphosphatase regulates glucose-stimulated insulin secretion of mouse pancreatic beta-cells.

Pancreatic ß-cells can precisely sense glucose stimulation and accordingly adjust their insulin secretion. Fructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme, but its physiological significance in ß-cells is not established. Here we determined its physiological role in regulating glucose sensing and insulin secretion of ß-cells. Considerable FBPase mRNA was detected in normal mouse islets and ß-cell lines, although their protein levels appeared to be quite low. Down-regulation of FBP1 in MIN6 cells by small interfering RNA could enhance the glucose-stimulated insulin secretion (GSIS), whereas FBP1-overexpressing MIN6 cells exhibited decreased GSIS. Inhibition of FBPase activity in islet ß-cells by its specific inhibitor MB05032 led to significant increase of their glucose utilization and cellular ATP to ADP ratios and consequently enhanced GSIS in vitro. Pretreatment of mice with the MB05032 prodrug MB06322 could potentiate GSIS in vivo and improve their glucose tolerance. Therefore, FBPase plays an important role in regulating glucose sensing and insulin secretion of ß-cells and serves a promising target for diabetes treatment.

Zbtb20 is essential for the specification of CA1 field identity in the developing hippocampus.

The development of hippocampal circuitry depends on the proper assembly of correctly specified and fully differentiated hippocampal neurons. Little is known about factors that control the hippocampal specification. Here, we show that zinc finger protein Zbtb20 is essential for the specification of hippocampal CA1 field identity. We found that Zbtb20 expression was initially activated in the hippocampal anlage at the onset of corticogenesis, and persisted in immature hippocampal neurons. Targeted deletion of Zbtb20 in mice did not compromise the progenitor proliferation in the hippocampal and adjacent transitional ventricular zone, but led to the transformation of the hippocampal CA1 field into a transitional neocortex-like structure, as evidenced by cytoarchitectural, neuronal migration, and gene expression phenotypes. Correspondingly, the subiculum was ectopically located adjacent to the CA3 in mutant. Although the field identities of the mutant CA3 and dentate gyrus (DG) were largely maintained, their projections were severely impaired. The hippocampus of Zbtb20 null mice was reduced in size, and exhibited increased apoptotic cell death during postnatal development. Our data establish an essential role of Zbtb20 in the specification of CA1 field identity by repressing adjacent transitional neocortex-specific fate determination.

[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.

[Genetic association of apoE and apoCI gene polymorphisms with coronary heart disease].

OBJECTIVE: To study the genetic association of apolipoprotein (apo) E and apoCI gene polymorphisms with coronary heart disease (CHD) in China. METHODS: apoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the apoCI promoter polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 186 cases with CHD (age: 65.0 +/- 10.5 years) and 350 controls (age: 63.6 +/- 8.3 years). The haplotype frequencies were estimated. RESULTS: The frequencies of apoE E4/3 genotype (26.9%) and epsilon4 (14.5%) in CHD group were significantly higher than that in the control group (12.6%, 7.0%), P <0.05. The significant difference was also found for the apoCI locus and the CHD group showed higher rate of both for the H2 allele and genotypes, carrying this allele. Estimation of the haplotype frequencies indicated that the association between the apoE-CI haplotype and CHD was significantly strong. The apoE-epsilon4/apoCI-H2 was estimated to be responsible for 9.86% of CHD. CONCLUSION: When the subjects carrying both epsilon4 and H2 alleles, they would have higher risk of suffering from CHD than controls.