Genotype-environment interaction on arterial stiffness: A pedigree-based study / 北京大学学报(医学版)

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.

Genetic evidence for the onset and development of myopia / 中华实验眼科杂志

Myopia is a common refractive eye disease, which is an ametropia in which the spherical equivalent of the eye is less than or equal to -0.50 D, or the axial length of the eye is more than 24 mm.As myopia progresses, the likelihood of ocular complications gradually increases, including retinal detachment, retinal neovascularization, macular degeneration, and other pathological changes.In recent years, the annual incidence of myopia has increased significantly and has become the second leading cause of blindness worldwide.Epidemiologic studies have shown that the distribution of myopia presents obvious ethnic differences and familial clustering characteristics, indicating that genetic factors play an important role in the onset and development of myopia.In addition, researchers have identified many pathogenic variants and candidate genes for myopia in patient samples, revealing the genetic and molecular mechanisms of myopia development.The genetic factor not only can serve as the independent factor that affects myopia development but also can interact with the environmental factor and together control the progression of myopia.This article reviewed the epidemiological research evidence on the heritability of myopia, the genetic factors of myopia development, and the interaction between genetic and environmental factors to provide new ideas for the prevention, control and treatment of myopia.

HLA-G 3’UTR polymorphisms & response to a yoga-based lifestyle intervention in rheumatoid arthritis: A randomized controlled trial

Background & objectives: Human leucocyte antigen (HLA)-G plays a vital role in immunomodulation in rheumatoid arthritis (RA). The mounting evidence suggests a link between HLA-G gene polymorphisms, disease susceptibility and methotrexate treatment response. Various environmental factors influence the onset and progression of RA and its treatment outcomes. The aim is to identify the treatment response of HLA-G 3’ untranslated region polymorphisms to yoga-based lifestyle intervention (YBLI). Methods: In this eight-week single-blinded randomized controlled trial (CTRI/2017/05/008589), patients with RA (n=140) were randomized into two groups namely, yoga group or non-yoga group. Baseline genomic DNA was isolated using salting-out method. PCR-based methods were used for genotyping. The levels of soluble (s) HLA-G and disease activity were assessed by ELISA and disease activity score-28–erythrocyte sedimentation rate (DAS28-ESR), respectively, at baseline (day 0) and after eight weeks of intervention. Results: Low-producing sHLA-G genotypes, i.e. +3142GG and 14 bp ins/ins, showed a significant increase in sHLA-G levels after YBLI. The association analysis between HLA-G polymorphisms and treatment for RA showed no considerable differential treatment remission in either of the groups (P>0.05). The percentages of improvement were higher in the yoga group as compared to the non-yoga group in both the HLA-G +3142G>C and 14 bp ins/del polymorphisms irrespective of their respective genotypes. No significant association was found between sHLA-G levels and disease activity with respect to genotypes. Interpretation & conclusions: Yoga intervention results in improvement and reduced severity of RA in patients irrespective of the HLA-G 14 bp ins/del or +3142G>C polymorphisms. YBLI may be used as an adjunct therapy in RA independent of the genotypes

Gene-environment interactions related to maternal exposure to environmental and lifestyle-related chemicals during pregnancy and the resulting adverse fetal growth: a review

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.

Effect of hOGG1 gene polymorphisms on urinary 8-OHdG level in occupational chromate exposed population / 中国职业医学

OBJECTIVE: To evaluate the genetic damage induced by occupational chromate exposure, and to analyze the association between human 8-oxoguanine-DNA N-glycosylase 1(hOGG1) polymorphisms and genetic damage in population with chromate exposure. METHODS: A total of 136 chromate exposed workers were recruited as exposure group by judgmental sampling method, and 156 workers without chromate and other occupational hazard factors exposure were recruited as control group. The whole blood chromium(WB-Cr) level was measured by inductively coupled plasma mass spectrometry. Urinary 8-hydroxy-2′-deoxyguanosine(8-OHdG) was determined by enzyme-linked immunosorbent assay. Four single nucleotide polymorphisms of hOGG1 gene were genotyped by the matrix assisted laser desorption ionization/time of flight mass spectrometry. RESULTS: The WB-Cr level was higher in the exposure group than that in the control group(meclian: 3.41 vs 0.90 μg/L, P<0.01). The urinary 8-OHdG level was higher in the exposure group compared with that in the control group(meclian: 6.02 vs 4.72 μg/g·creatinine, P<0.01). In study subjects(exposure group and control group), after adjusting the potential influencing factors such as age, body mass index(BMI), gender, smoking and drinking, chromate exposure might be a risk factor for increasing urinary 8-OHdG level(P<0.05), and the recessive models of rs293796 and rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05). In chromate exposure group, the additive and recessive models of rs293796 and the recessive model of rs13096551 were observed as risk factors of increasing urinary 8-OHdG level(P<0.05), while the dominant model of rs3219008 was protective factor of increasing urinary 8-OHdG level(P<0.05), after adjusting the potential influencing factors such as age, BMI, gender, smoking, drinking. However, after multiple Bonferroni correction tests, only the recessive model of rs293796 was the risk factor of increasing urinary 8-OHdG level in the exposed group(P<0.01). There was significant interaction between chromate exposure and rs293796 on urinary 8-OHdG(P<0.01). CONCLUSION: The rs13096551 and rs293796 of hOGG1 were associated with the alteration of urinary 8-OHdG level induced by chromate. There was interaction between rs294796 of hOGG1 and chromate exposure on urinary 8-OHdG level.

Predicting Behavior Problems in Korean Preschoolers: Interactions of the SLC6A4 Gene and Maternal Negative Affectivity

OBJECTIVE: This study aimed to investigate whether maternal negative affectivity (MNA) moderates the effect of genetic polymorphism of SLC6A4 on behavior problems in children. METHODS: Study participants comprised 143 preschoolers and their mothers from South Korea. The Childhood Behavior Checklist and Emotionality, Activity, and Sociability adult scale were used to measure child behavior and maternal affectivity. DNA from saliva was genotyped to determine serotonin transporter polymorphism. RESULTS: MNA appeared to exert effects in externalizing (b=5.78, p<0.001) and internalizing problems (b=6.09, p< 0.001). Interaction between SLCA4 polymorphism and MNA showed effects on externalizing (b=−7.62, p<0.01) and internalizing problems (b=−9.77, p<0.01). Children with two short alleles showed considerable differences in both externalizing and internalizing problems according to MNA; however, children with one short allele or none showed relatively few differences in behavior problems due to maternal affectivity. CONCLUSION: The effect of SLC6A4 polymorphism on child behavior seemed to be moderated by MNA. In addition, the impact of MNA was found to vary based on a child’s genetic risk. High MNA may trigger the risk allele while low MNA causes the risk allele to illicit less behavior problems. Children with two short variants of the SLC6A4 gene may benefit from intervention that modulates MNA.

Family History, Tobacco Smoking, and Risk of Ischemic Stroke / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Both genetic factors and smoking are associated with ischemic stroke (IS) risk. However, little is known about the potential interaction of these factors. We aimed to assess whether smoking and a positive family history interact to increase the risk of IS. METHODS: The nationwide prospective study recruited 210,000 men and 300,000 women in 2004 to 2008 at ages 30 to 79 years. During 9.7 years of follow-up, we documented 16,923 and 20,656 incident IS cases in men and women without major chronic diseases at baseline, respectively. Multivariable Cox regression models were used to examine associations between family history and IS. Likelihood ratio tests were used to test the smoking-family history interactions on IS. RESULTS: About 67.8% (n=135,168) of men ever smoked regularly compared with 2.7% (n=7,775) of women. Among men, a significant interaction between family history and smoking on IS was observed (P for interaction=0.03), with more pronounced association between family history and IS among ever-regular smokers (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.16 to 1.27) than among never-smokers (HR, 1.11; 95% CI, 1.01 to 1.23). The association between family history and IS among ex-smokers after more than 10 years of cessation (HR, 1.01; 95% CI, 0.85 to 1.20) appeared similar to that among never-smokers. Among women, a similar but not significant interaction between family history and smoking on IS was observed. Ever-regular smokers who had a family history of stroke had the highest risk of IS. CONCLUSIONS: Among Chinese men, the association of family history with IS was accentuated by smoking, and such accentuation tended to be lowered by cessation.

Identification of susceptibility genes for osteoporosis through interaction between smoking and genetic factors / 西安交通大学学报(医学版)

Objective To make a systematic analysis of the interaction between osteoporosis and smoking to elucidate the molecular mechanisms underlying osteoporosis susceptibility affected by smoking.Methods First,a two-way ANOVA analysis was conducted using microarray data to search all potential genes associated with both smoking and osteoporosis.We further explored the potential biologically related metabolic pathways through gene pathway enrichment analysis.Then the interaction genes within enriched pathways were verified by genome-wide gene-environment interaction analysis.Finally,protein-protein interaction analysis was applied to identify the core regulatory network in which those verified genes involved.Results We identified 441 risk genes closely associated with both smoking and osteoporosis by microarray analysis.Through gene pathway analysis,we identified a vital metabolism pathway, gap junction, which is a potential mediator between smoking and osteoporosis process. Finally,we verified some critical genes by genome-wide gene-environment interaction analysis,and revealed a potential smoking-osteoporosis interaction core regulatory network that included 1 3 proteins by protein network analysis.Conclusion We have discovered a new regulatory framework connecting smoking and osteoporosis, which provides new clues about disease etiologies and novel promising drug targets.

Necessity of Epigenetic Epidemiology Studies on the Carcinogenesis of Lung Cancer in Never Smokers / 예방의학회지

Based on epidemiological and genomic characteristics, lung cancer in never smokers (LCNS) is a different disease from lung cancer in smokers. Based on current research, the main risk factor for LCNS may be air pollution. A recent case-control study in Koreans reported that nitrogen dioxide (NO₂) may be a risk factor for LCNS. Additionally, a cohort study showed that exposure to NO2 was associated with significant hypomethylation. Thus, epigenetic epidemiology studies are needed in the near future to evaluate the carcinogenesis of LCNS according to chronic exposure to air pollution and/or viral infections.

Evolutionary Psychiatry I-Concept of Evolutionary Psychology and Evolutionary Psychopathology / 신경정신의학

The evolutionary theory is applied to explain a multitude of natural and social phenomena. In medicine, evolutionary biology and psychology enables us to take perspectives beyond the biomedical paradigm of disease. The evolutionary pathophysiology looks for the ultimate cause of disease rather than the proximate causes. The ultimate cause of disease lies in the evolved psychological mechanisms (EPMs). This recognition fundamentally alters the traditional view of pathogenesis that a disease is the result of alien pathogens invading our bodies. Especially in psychiatry, the insight that the pathologic and normal mind have a common basis and that discriminating between them solely by means of natural science is rather impossible, this makes us rethink the validity of current reductionistic approaches to psychiatric nosology. In this article (Part I), the authors introduce evolutionary biology and psychology. Detailed application of the evolutionary perspective to psychiatric disorders will be discussed in the continuing article (Part II).

Interpretation of the hygiene and microflora hypothesis for allergic diseases through epigenetic epidemiology / 한국역학회지

The hygiene hypothesis (HH) proposed by Strachan in 1989 was expanded to explain the inverse association between the occurrence of allergy disorders and the risk of infectious diseases and parasite infestation. The microflora hypothesis (MH) suggests that gut microbial dysbiosis in early life might trigger hypersensitivity disorders. The sharing concept of both HH and MH is gene-environment interaction, which is also a key concept in epigenetics. The amalgamation of epidemiology and epigenetics has created a scientific discipline termed epigenetic epidemiology. To accomplish an era of gene-environment-wide interaction studies, it is necessary to launch a national human epigenome project.

Interpretation of the hygiene and microflora hypothesis for allergic diseases through epigenetic epidemiology / 한국역학회지

The hygiene hypothesis (HH) proposed by Strachan in 1989 was expanded to explain the inverse association between the occurrence of allergy disorders and the risk of infectious diseases and parasite infestation. The microflora hypothesis (MH) suggests that gut microbial dysbiosis in early life might trigger hypersensitivity disorders. The sharing concept of both HH and MH is gene-environment interaction, which is also a key concept in epigenetics. The amalgamation of epidemiology and epigenetics has created a scientific discipline termed epigenetic epidemiology. To accomplish an era of gene-environment-wide interaction studies, it is necessary to launch a national human epigenome project.

Relationship between XPD, RAD51, and APEX1 DNA repair genotypes and prostate cancer risk in the male population of Rio de Janeiro, Brazil

Abstract Susceptibility to cancer ensues in individuals carrying malfunctioning DNA repair mechanisms. The impact of Single Nucleotide Polymorphisms (SNPs) in key DNA repair mechanisms on risk for prostate cancer was investigated in this case-control study. Samples consisted of 110 patients with confirmed prostate cancer and 200 unaffected men, from Rio de Janeiro, Brazil. XPD/Lys751Gln (rs13181), APEX1/Asp148Glu (rs1130409), and RAD51/G135C (rs1801320) SNPs were analyzed by PCR-RFLP. Allelic and genotypic frequencies were calculated and compared by Chi-Square test. The association between SNPs and clinical/epidemiological data was considered significant by Odds Ratio analysis, with IC95% and a p-value≤0.05. Only the XPD/Lys751Gln SNP significantly increased susceptibility to disease in southeastern Brazilian men, with p≤0.001 [OR=2.36 (1.46-3.84)], with no association with APEX1 or RAD51 SNPs. Combined XPD+RAD51 SNPs were highly associated with the disease, p≤0.005 [OR=3.40 (1.32-9.20)]. A Chi-Square significant association between XPD/Lys751Gln and Gleason score was also observed (OR=9.31; IC95%=1.19-428.0; p=0.022). Epidemiological inquiries revealed that exposure to pesticides significantly impacted the risk for prostate cancer in this population. DNA repair dysfunctions seem to prevail among workers exposed to chemical byproducts to cancer in this specific tissue. Non-invasive genotyping SNPs may help assessment of prostate cancer risk in environmentally exposed populations.

Genetic Signatures of Asthma Exacerbation

Asthma exacerbation (AE) usually denotes worsening of asthma symptoms that requires intense management to prevent further deterioration. AE has been reported to correlate with clinical and demographic factors, such as race, gender, and treatment compliance as well as environmental factors, such as viral infection, smoking, and air pollution. In addition, recent observations suggest that there are likely to be genetic factors specific to AE. Understanding genetic factors specific to AE is essential to develop therapy tailored for exacerbation-prone asthma. Here, we summarize the results of studies involving genetic risk factors for AE. To simplify and enhance understanding, we reviewed the studies according to the following categories: hypothesis-driven approaches, hypothesis-free approaches, gene-environment interactions, and pharmacogenetics.

Effects of Soy Product Intake and Interleukin Genetic Polymorphisms on Early Gastric Cancer Risk in Korea: A Case-Control Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The current study investigated whether the combined effects of soy intake and genetic polymorphisms of interleukin (IL) genes modify gastric cancer risk. MATERIALS AND METHODS: A total of 377 cases and 754 controls of Korean origin were included in the analysis. Soy consumption was assessed using a semi-quantitative food frequency questionnaire. Seven variants of IL10 (rs1800871), IL2 (rs2069763 and rs2069762), IL13 (rs6596090 and rs20541), and IL4R (rs7205663 and rs1805010) were genetically analyzed. To analyze the combined effect of soy intake and genetic polymorphisms, a low-intake group and high-intake group of each type of soy were categorized based on the intake level of the control group. Interactions between soy products and these genetic variants were analyzed by a likelihood ratio test, in which a multiplicative interaction term was added to the logistic regression model. RESULTS: A higher intake of nonfermented soy products was associated with a reduced cancer risk (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.43 to 0.90), and the reduced risk was only apparent in males (OR, 0.44; 95% CI, 0.27 to 0.71). None of the IL genetic polymorphisms examined were independently associated with gastric cancer risk. Individuals with a minor allele of IL2 rs2069762 and a higher intake of nonfermented soy food had a decreased risk of gastric cancer (OR, 0.46; 95% CI, 0.31 to 0.68) compared to those with a lower intake (p(interaction)=0.039). CONCLUSION: Based on the genetic characteristics of the studied individuals, the interaction between IL2 rs2069762 and nonfermented soy intake may modify the risk of gastric cancer.

RORA Polymorphism Interacts with Childhood Maltreatment in Determining Anxiety Sensitivity by Sex: A Preliminary Study in Healthy Young Adults

OBJECTIVE: Recent studies have reported associations of retinoid-related orphan receptor alpha (RORA) gene single nucleotide polymorphisms (SNPs) with depression and anxiety disorders. Based on these, we attempt to test whether RORA polymorphism is associated with anxiety sensitivity (AS), the intermediate phenotype of depression and anxiety disorders. Considering gene-environment interactions and sex differences in AS, childhood maltreatment (CM) and sex were considered as confounders. METHODS: Two-hundred and five healthy young Korean adults (female: 98, male: 107; age, 23.0±3.2 years) completed genotyping for the RORA SNP rs11071547, as well as measures for AS and CM. Generalized linear models were used to examine the main and interaction effects of RORA genotype, CM, and sex in determining AS. RESULTS: The main effect of RORA polymorphisms was not found (p=0.760) whereas the main effect of CM and interaction effects among sex, genotype, and maltreatment were significant on AS. In separate analyses by sex, the interaction effect between RORA genotype and maltreatment was significant only in males (p < 0.001). In females, the main effects of genotype and CM were significant (both were p < 0.001), in which both a history of CM and C genotype tended to be associated with higher AS. CONCLUSION: The association between RORA polymorphism and AS might differ by sex. The interaction between RORA polymorphism and CM was significant only in males whereas RORA genotype and CM independently associated with AS in females. Further studies are encouraged to confirm the relationship between RORA polymorphism and AS.

Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

Background & objectives: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. Methods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. Results: All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. Interpretation & conclusions: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.

Association of organochlorine pesticides with the mRNA expression of tumour necrosis factor-alpha (TNF-α) & cyclooxygenase-2 (COX-2) genes in idiopathic preterm birth.

Background & objectives: Preterm birth (PTB) is an important cause of prenatal death, neonatal morbidity and mortality and adult illness. Increased inflammation occurs in normal parturition, and inflammatory cytokines and oxidative stress are found to be higher in PTB cases. The present study was planned to investigate the association of organochlorine pesticides (OCPs) with mRNA expression of inflammatory pathway genes such as tumour necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in preterm delivery (PTD) cases. Methods: Maternal blood samples of PTD (n=30) cases and equal number of term delivery (n=30) were collected at the time of labour. Women occupationally exposed to OCPs and other high risk factors such as anaemia, hypertension, bacterial vaginosis, renal and heart disease, diabetes, etc. were excluded. The OCP levels were estimated by gas chromatography, and mRNA expressions of TNF-α and COX-2 genes were analysed using real-time PCR (qPCR). Results: Significantly higher levels of β-HCH (beta-hexachlorocyclohexane, 95% CI=2.08-4.633, P=0.001), p’p’-DDE (para, para-dichlorodiphenyldichloroethylene, 95% CI=0.546-2.551, P=0.003), and o’p’-DDD (ortho, para-dichlorodiphenyldichloroethane, 95% CI=0.004-0.690, P=0.047) were observed in maternal blood of PTB cases as compared to term delivery. The mRNA expressions of COX-2 and TNF-α genes were 3.13 and 2.31 folds higher in PTB cases in comparison to term delivery. Linear positive correlations were observed between period of gestation (POG) and ΔCt of COX-2 and TNF-α genes. Interpretation & conclusions: Environmental factors such as OCPs may be associated with inflammatory events showing gene-environment interaction in PTB cases. Evaluating the molecular control of inflammation along with gene environment interaction may be used as a model to explore the aetiology of idiopathic PTB cases and may be considered for the prognosis of adverse reproductive outcomes.

Interaction of lipoprotein lipase polymorphisms with body mass index and birth weight to modulate lipid profiles in children and adolescents: the CASPIAN-III Study / Interação de polimorfismos da lipoproteína lipase com índice de massa corporal e peso ao nascer para modular o perfil lipídico em crianças e adolescentes: o estudo CASPIAN-III

CONTEXT AND OBJECTIVE: Interactions between body mass index (BMI), birth weight and risk parameters may contribute to diseases rather than the individual effects of each factor. However this hypothesis needs to be confirmed. This study aimed to determine to what extent variants of lipoprotein lipase (LPL) might interact with birth weight or body weight in determining the lipid profile concentrations in children and adolescents. DESIGN AND SETTING: Substudy of the third survey of a national surveillance system (CASPIAN-III Study) in Iran. METHODS: Whole blood samples (kept frozen at -70 °C) were randomly selected from 750 students aged 10-18 years. Real-time polymerase chain reaction (PCR) and high-resolution melt analysis were performed to assess S447X (rs328), HindIII (rs320) and D9N (rs1801177) polymorphisms. RESULTS: The AG/GG genotype in D9N polymorphism was associated with higher LDL-C (low-density lipoprotein cholesterol) and lower HDL-C (high-density lipoprotein cholesterol) concentration. Significant interactions were found for D9N polymorphism and birth weight in association with plasma HDL-C concentration, and also for D9N polymorphism and BMI in association with plasma triglyceride (TG) and HDL-C levels. HindIII polymorphism had significant association with birth weight for HDL-C concentration, and with BMI for TG and HDL-C levels. Significant interactions were found for S447X polymorphism and BMI in association with plasma TG and HDL-C concentrations. CONCLUSION: We found significant interactive effects from LPL polymorphisms and birth weight on HDL-C concentration, and also effects from LPL polymorphisms and BMI on TG and HDL-C concentrations.

RESUMO CONTEXTO E OBJETIVO: Interações entre índice de massa corporal (IMC), peso ao nascer e parâmetros de risco podem contribuir para doenças, em vez de efeitos individuais de cada fator. No entanto, essa hipótese precisa de confirmação. Este estudo visou determinar o quanto variantes de lipoproteína lipase (LPL) podem interagir com peso de nascimento ou peso corporal na determinação das concentrações do perfil lipídico em crianças e adolescentes. DESENHO E LOCAL: Sub-estudo da terceira pesquisa de sistema nacional de vigilância (Estudo CASPIAN-III) no Irã. MÉTODOS: Foram selecionadas aleatoriamente amostras de sangue total (mantidas congeladas a -70 °C) de 750 estudantes com idades entre 10-18 anos. Reação de polimerase em cadeia (PCR) em tempo real e análise de fusão de alta resolução foram realizados para avaliar polimorfismo de S447X (rs328), HindIII (rs320) e D9N (rs1801177). RESULTADOS: Genótipo AG/GG em polimorfismo D9N foi associado com concentração maior de LDL-C (colesterol do tipo lipoproteína de baixa densidade) e menor de HDL-C (colesterol do tipo lipoproteína de alta densidade). Interações significativas foram encontradas para polimorfismo D9N e peso ao nascer em associação com concentração plasmática de HDL-C, bem como para polimorfismo D9N e IMC em associação com níveis plasmáticos de triglicérides (TG) e HDL-C. Polimorfismo HindIII teve associação significativa com peso de nascimento para concentração de HDL-C, e com IMC para níveis de TG e HDL-C. Interações significativas foram encontradas para polimorfismo S447X e IMC em associação com concentrações plasmáticas de TG e HDL-C. CONCLUSÃO: Encontramos efeitos interativos significativos de polimorfismo LPL e peso de nascimento sobre concentração de HDL-C, bem como efeitos de polimorfismos LPL e IMC sobre concentrações de TG e HDL-C.

Replication of Early B-cell Factor 1 (EBF1) Gene-by-psychosocial Stress Interaction Effects on Central Adiposity in a Korean Population / 예방의학회지

OBJECTIVES: Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels. We aimed to evaluate EBF1 gene-by-stress interaction effects on central adiposity traits, including visceral adipose tissue (VAT), in Korean adults. METHODS: A total of 1467 Korean adults were included in this study. We selected 22 single-nucleotide polymorphisms (SNPs) in the EBF1 gene and analyzed their interactions with stress on central adiposity using additive, dominant, and recessive genetic modeling. RESULTS: The four SNPs that had strong linkage disequilibrium relationships (rs10061900, rs10070743, rs4704967, and rs10056564) demonstrated significant interactions with the waist-hip ratio in the dominant model (p(int)<0.007). In addition, two other SNPs (rs6556377 and rs13180086) were associated with VAT by interactions with stress levels, especially in the recessive genetic model (p(int)<0.007). As stress levels increased, the mean values of central adiposity traits according to SNP genotypes exhibited gradual but significant changes (p<0.05). CONCLUSIONS: These results suggest that the common genetic variants for EBF1 are associated with central adiposity through interactions with stress levels, emphasizing the importance of managing stress in the prevention of central obesity.