BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

OBJECTIVE: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. METHODS: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. RESULTS: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. CONCLUSION The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.
Humans ; Male ; Middle Aged ; Female ; Ankle Brachial Index ; Cohort Studies ; Gene-Environment Interaction ; Vascular Stiffness/genetics* ; Pedigree ; Pulse Wave Analysis/methods* ; Genotype

Humans ; Diabetes Mellitus, Type 2/genetics* ; Gene-Environment Interaction ; Polymorphism, Single Nucleotide

Biogenetics plays an important role in the pathogenesis of depressive disorder in adolescents. Various genetic polymorphism studies have updated the understanding of adolescent depressive disorder. However, due to the influence of gene-environment interaction and age of puberty, the influence of gene polymorphisms on adolescent depressive disorder is complicated to clarify. Investigating and clarifying the relationship between gene polymorphisms and adolescent depressive disorder will promote the research on the pathogenesis of this disorder and provide a reference for the prevention and treatment of this disorder. This article reviews the genetic polymorphisms related to adolescent depressive disorder.
Humans ; Adolescent ; Depressive Disorder, Major/genetics* ; Polymorphism, Genetic ; Gene-Environment Interaction ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease

BACKGROUND: There are only limited numbers of reviews on the association of maternal-child genetic polymorphisms and environmental and lifestyle-related chemical exposure during pregnancy with adverse fetal growth. Thus, this article aims to review: (1) the effect of associations between the above highlighted factors on adverse fetal growth and (2) recent birth cohort studies regarding environmental health risks. METHODS: Based on a search of the PubMed database through August 2021, 68 epidemiological studies on gene-environment interactions, focusing on the association between environmental and lifestyle-related chemical exposure and adverse fetal growth was identified. Moreover, we also reviewed recent worldwide birth cohort studies regarding environmental health risks. RESULTS: Thirty studies examined gene-smoking associations with adverse fetal growth. Sixteen maternal genes significantly modified the association between maternal smoking and adverse fetal growth. Two genes significantly related with this association were detected in infants. Moreover, the maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1), X-ray repair cross-complementing protein 3 (XRCC3), interleukin 6 (IL6), interleukin 1 beta (IL1B), human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1), HLA DQ beta 1 (HLA-DQB1), and nicotinic acetylcholine receptor. Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1) and fat mass and obesity-associated protein (FTO). Thirty-eight studies examined the association between chemical exposures and adverse fetal growth. In 62 of the 68 epidemiological studies (91.2%), a significant association was found with adverse fetal growth. Across the studies, there was a wide variation in the analytical methods used, especially with respect to the genetic polymorphisms of interest, environmental and lifestyle-related chemicals examined, and the study design used to estimate the gene-environment interactions. It was also found that a consistently increasing number of European and worldwide large-scale birth cohort studies on environmental health risks have been conducted since approximately 1996. CONCLUSION There is some evidence to suggest the importance of gene-environment interactions on adverse fetal growth. The current knowledge on gene-environment interactions will help guide future studies on the combined effects of maternal-child genetic polymorphisms and exposure to environmental and lifestyle-related chemicals during pregnancy.
Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Female ; Fetal Development ; Gene-Environment Interaction ; Humans ; Life Style ; Maternal Exposure/adverse effects* ; Polymorphism, Genetic ; Pregnancy

The incidence of obesity in our country is increasing year by year. Diet and lifestyle interventions are the most commonly used weight loss measures, but their intervention effects are affected by individual genetics, environment and other factors. Genome-wide association analysis has found many SNPs related to weight loss, and explored the interaction between these loci and diet, intestinal flora and other environmental factors. This article summarizes the study of single nucleotide polymorphisms, the analysis of gene-environment interactions related to diet interventions for weight loss, and the multi-loci analysis and prediction models such as genetic risk scores and machine learning modeling in weight loss, which provides reference for the further application and development of the precise nutrition in medical weight loss.
Gene-Environment Interaction ; Genome-Wide Association Study ; Humans ; Life Style ; Obesity/prevention & control* ; Polymorphism, Single Nucleotide

Alzheimer Disease/genetics* ; Animals ; Apolipoprotein E4/metabolism* ; Gene-Environment Interaction ; Hippocampus/metabolism* ; Male ; Noise/adverse effects* ; Rats

OBJECTIVE: Depression is associated with various environmental risk factors such as stress, childhood maltreatment experiences, and stressful life events. Current approaches to assess the pathophysiology of depression, such as epigenetics and gene-environment (GxE) interactions, have been widely leveraged to determine plausible markers, genes, and variants for the risk of developing depression. METHODS: We focus on the most recent developments for genomic research in epigenetics and GxE interactions. RESULTS: In this review, we first survey a variety of association studies regarding depression with consideration of GxE interactions. We then illustrate evidence of epigenetic mechanisms such as DNA methylation, microRNAs, and histone modifications to influence depression in terms of animal models and human studies. Finally, we highlight their limitations and future directions. CONCLUSION: In light of emerging technologies in artificial intelligence and machine learning, future research in epigenetics and GxE interactions promises to achieve novel innovations that may lead to disease prevention and future potential therapeutic treatments for depression.
Artificial Intelligence ; Biomarkers ; Depression ; DNA Methylation ; Epigenomics ; Gene-Environment Interaction ; Histone Code ; Humans ; Machine Learning ; MicroRNAs ; Models, Animal ; Risk Factors

Cancer is a complex, heterogeneic, and dynamic disease involving multiple gene-environment interactions, and affecting numerous biological pathways. As such, the development of reliable and robust non-invasive platforms constitutes a vital step toward realizing the potential of precision medicine. Distant metastases harbor unique genomic characteristics that are not detectable in the corresponding primary tumor of the same patient, and metastases located at different sites show considerable intra-patient heterogeneity. Thus, the analysis of the resected primary tumor alone or, if possible, re-evaluation of tumor characteristics based on the biopsy of the most accessible metastasis, may not reveal sufficient information for treatment decisions. Here, we propose that this dilemma can be solved by a new diagnostic concept: liquid biopsy, that is, the analysis of therapeutic targets and drug resistance-conferring gene mutations in or on circulating tumor cells (CTCs). Finally, the analysis of the resected primary tumor alone may provide misleading information with regard to the characteristics of metastases, the key target for systemic anticancer therapy. Liquid biopsies are noninvasive tests using blood or fluids that detect CTCs or the products of tumors, such as fragments of nucleotides or proteins that are shed into biological fluids from the primary or metastatic tumors. Such biopsies are expected to be informative or easily accessible tools to provide comprehensive information regarding cancers beyond conventional biopsies. Thus, this review addresses the use of CTCs in cancer detection, diagnosis and monitoring and discusses the direction of its clinical application in cancer patient care.
Biopsy ; Diagnosis ; Early Detection of Cancer ; Gene-Environment Interaction ; Humans ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Nucleotides ; Patient Care ; Population Characteristics ; Precision Medicine

OBJECTIVE: To investigate the association of genetic polymorphisms of norepinephrine metabolizing enzymes with postpartum depression and analyze the risk factors for postpartum depression in women following cesarean section. METHODS: A total of 591 Chinese woman of Han Nationality undergoing caesarean section were enrolled in this study. The diagnosis of postpartum depression was established for an Edinburgh Postnatal Depression Scale (EPDS) score ≥9. For all the women without antepartum depression, the genotypes of catechol-O-methyltransferase (COMT; at 5 sites including rs2020917 and rs737865) and monoamine oxidase A (rs6323) were determined using Sequenom Mass Array single nucleotide polymorphism (SNP) analysis. We analyzed the contribution of the genetic factors (SNPs, linkage disequilibrium and haplotype) to postpartum depression and performed logistic regression analysis to identify all the potential risk factors for postpartum depression and define the interactions between the genetic and environmental factors. RESULTS: The incidence of postpartum depression was 18.1% in this cohort. Univariate analysis suggested that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype) were significantly correlated with the occurrence of postpartum depression ( < 0.05). Logistic regression analysis showed that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype), severe stress during pregnancy, and domestic violence were the risk factors for postpartum depression ( < 0.05); no obvious interaction was found between the genetic polymorphisms and the environmental factors in the occurrence of postpartum depression. CONCLUSIONS The rs2020917TT and rs737865GG genotypes of COMT, stress in pregnancy, and domestic violence are the risk factors for postpartum depression.
Catechol O-Methyltransferase ; genetics ; Cesarean Section ; adverse effects ; Depression, Postpartum ; diagnosis ; enzymology ; genetics ; Domestic Violence ; psychology ; Female ; Gene-Environment Interaction ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Monoamine Oxidase ; genetics ; Norepinephrine ; metabolism ; Polymorphism, Single Nucleotide ; Postoperative Complications ; diagnosis ; enzymology ; genetics ; Pregnancy ; Pregnancy Complications ; etiology ; psychology ; Risk Factors ; Stress, Psychological