Haplotype analysis on correlation between transcription factor 7-like 2 gene polymorphism and breast cancer risk

Abstract Background Up to now, limited researches focused on the association between transcription factor 7-like 2 gene (TF7L2) gene single nucleotide polymorphisms (SNPs) and breast cancer (BC) risk. The aim of this study was to evaluate the associations between TF7L2 and BC risk in Chinese Han population. Methods Logistic regression model was used to test the correlation between polymorphisms and BC risk. Strength of association was evaluated by odds ratio (OR) and 95% confidence interval (CI). Generalized multifactor dimensionality reduction (GMDR) was applied to analyze the SNP-SNP and gene-environment interaction. Results Logistic regression analysis indicated that the BC risk was obviously higher in carriers of rs1225404 polymorphism C allele than that in TT genotype carriers (TC or CC versus TT), adjusted OR (95%CI) =1.40 (1.09–1.72). Additionally, we also discovered that people with rs7903146- T allele had an obviously higher risk of BC than people with CC allele (CT or TT versus CC), adjusted OR (95%CI) =1.44 (1.09–1.82). GMDR model was used to research the effect of interaction among 4 SNPs and environmental factors on BC risk. We discovered an important two-locus model (p = 0.0100) including rs1225404 and abdominal obesity, suggesting a potential gene–environment correlation between rs1225404 and abdominal obesity. In general, the cross-validation consistency of two-locus model was 10 of 10, and the testing accuracy was 0.632. Compared with subjects with normal waist circumference (WC) value and rs1225404 TT genotype, abdominal obese subjects with rs1225404 TC or CC genotype had the highest BC risk. After covariate adjustment, OR (95%CI) was 2.23 (1.62–2.89). Haplotype analysis indicated that haplotype containing rs1225404-T and rs7903146-C alleles were associated with higher BC risk. Conclusions C allele of rs1225404 and T allele of rs7903146, interaction between rs1225404 and abdominal obesity, rs1225404-T and rs7903146-C haplotype were all related to increased BC risk.

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Transcription factor 7-like 2 gene- smoking interaction on the risk of diabetic nephropathy in Chinese Han population

Genes and Environment ◽

10.1186/s41021-021-00194-2 ◽

2021 ◽

Vol 43 (1) ◽

Author(s):

Peng Xue ◽

Haihong Cao ◽

Zhimin Ma ◽

Ying Zhou ◽

Nian Wang

Keyword(s):

Transcription Factor ◽

Logistic Regression ◽

Diabetic Nephropathy ◽

Chinese Han Population ◽

Environment Interaction ◽

Chinese Han ◽

Current Smoking ◽

Han Population ◽

Gene Environment ◽

The Relationship

Abstract Objectives To evaluate the relationship between transcription factor 7-like 2 (TCF7L2) gene polymorphism and diabetic nephropathy (DN) risk, as well as the effect of gene-environment interactions on DN risk in Chinese Han population. Methods The Hardy-Weinberg equilibrium (HWE) and the relationship between TCF7L2 gene single nucleotide polymorphism (SNPs) and DN susceptibility were evaluated by SNPStats. The interaction among four SNPs and environmental factors were tested by generalized multifactor dimensionality reduction (GMDR). The consistency of cross validation, accuracy of test balance and sign test were calculated to evaluate the interaction of each selection. The logistic regression was used to test the interaction between rs7903146 and current smoking by stratified analysis. Results Logistic regression analysis indicated that the DN risk of rs7903146-T allele carriers were obviously higher than that in CC genotype carriers (CT + TT versus CC), adjusted OR (95 %CI) = 1.64 (1.24–2.06). However, we also discovered that people with rs12255372, rs11196205 and rs290487 minor allele had non-significant difference risk of DN compared with people with major allele. The GMDR model found a significant two-locus model (p = 0.0100) including rs7903146 and current smoking, suggesting a potential gene–environment interaction between rs7903146 and current smoking. Compared with never smokers with rs7903146- CC genotype, current smokers with rs7903146- CT or TT genotype had the highest DN risk. After covariate adjustment, OR (95 %CI) was 2.15 (1.58–2.78). Conclusions We found a significant relationship of rs7903146-T alleles, and the interaction between rs7903146-T and current smoking with increased DN risk.

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Gene–gene and gene-environment interactions on cord blood total IgE in Chinese Han children

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00571-0 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Li Hua ◽

Quanhua Liu ◽

Jing Li ◽

Xianbo Zuo ◽

Qian Chen ◽

...

Keyword(s):

Environmental Factors ◽

Cord Blood ◽

Synergistic Effects ◽

Gene Interaction ◽

Independent Effect ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Gene Environment Interaction ◽

Gene Environment

Abstract Background IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. Methods 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. Results A four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2). Conclusions Gene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

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Evaluation of common variants in the CNR2 gene and its interaction with abdominal obesity for osteoporosis susceptibility in Chinese post-menopausal females

Bone and Joint Research ◽

10.1302/2046-3758.811.bjr-2018-0284.r1 ◽

2019 ◽

Vol 8 (11) ◽

pp. 544-549

Author(s):

W. Zheng ◽

C. Liu ◽

M. Lei ◽

Y. Han ◽

X. Zhou ◽

...

Keyword(s):

Logistic Regression ◽

Regression Model ◽

Abdominal Obesity ◽

Logistic Regression Model ◽

Haplotype Analysis ◽

Statistical Significance ◽

Chinese Patients ◽

Sign Test ◽

Environment Interaction ◽

Post Menopausal

Objectives The objective of this study was to investigate the association of four single-nucleotide polymorphisms (SNPs) of the cannabinoid receptor 2 (CNR2) gene, gene-obesity interaction, and haplotype combination with osteoporosis (OP) susceptibility. Methods Chinese patients with OP were recruited between March 2011 and December 2015 from our hospital. In this study, a total of 1267 post-menopausal female patients (631 OP patients and 636 control patients) were selected. The mean age of all subjects was 69.2 years (sd 15.8). A generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OP. For OP patient-control haplotype analyses, the SHEsis online haplotype analysis software ( http://analysis.bio-x.cn/ ) was employed. Results The logistic regression model revealed that the C allele of rs2501431 and the G allele of rs3003336 were associated with increased OP risk, compared with those with wild genotype. However, no significant correlations were found when analyzing the association of rs4237 and rs2229579 with OP risk. The GMDR analysis suggested that the interaction model composed of two factors, rs3003336 and abdominal obesity (AO), was the best model with statistical significance (p-value from sign test (Psign) = 0.012), indicating a potential gene-environment interaction between rs3003336 and AO. Overall, the two-locus models had a cross-validation consistency of 10/10 and had a testing accuracy of 0.641. Abdominally obese subjects with the AG or GG genotype have the highest OP risk, compared with subjects with the AA genotype and normal waist circumference (WC) (odds ratio (OR) 2.23, 95% confidence interval (CI) 1.54 to 3.51). Haplotype analysis also indicated that the haplotype containing the rs3003336-G and rs2501431-C alleles was associated with a statistically increased OP risk. Conclusion Our results suggested that the C allele of rs2501431 and the G allele of rs3003336 of the CNR2 gene, interaction between rs3003336 and AO, and the haplotype containing the rs3003336-G and rs2501431-C alleles were all associated with increased OP risk. Cite this article: Bone Joint Res 2019;8:544–549.

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Interaction between ELMO1 gene polymorphisms and environment factors on susceptibility to diabetic nephropathy in Chinese Han population

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-019-0492-0 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Yi Hou ◽

Yong Gao ◽

Yan Zhang ◽

Si-Tong Lin ◽

Yue Yu ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Alcohol Drinking ◽

Control Group ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Gene Environment Interaction ◽

Gene Environment ◽

Increased Risk ◽

Significant Gene

Abstract Background The association of diabetic nephropathy (DN) risk with single nucleotide polymorphisms (SNPs) within Engulfment and Cell Motility 1 (ELMO1) gene and gene–environment synergistic effect have not been extensively examined in, therefore, the purpose of this study is to explore the association between multiple SNPs in ELMO1 gene, and the relationship between gene–environment synergy effect and the risk of DN. Methods Genotyping for 4 SNPs was performed with polymerase chain reaction (PCR) and following restriction fragment length polymorphism (RFLP) methods. Hardy–Weinberg balance of the control group was tested by SNPstats (online software: http://bioinfo.iconologia.net/snpstats). The best combination of four SNPs of ELMO1 gene and environmental factors was screened by GMDR model. Logistic regression was used to calculating the OR values between different genotypes of ELMO1 gene and DN. Results The rs741301-G allele and the rs10255208-GG genotype were associated with an increased risk of DN risk, adjusted ORs (95% CI) were 1.75 (1.19–2.28) and 1.41 (1.06–1.92), respectively, both p-values were < 0.001. We also found that the others SNPs-rs1345365 and rs7782979 were not significantly associated with susceptibility to DN. GMDR model found a significant gene–alcohol drinking interaction combination (p = 0.0107), but no significant gene–hypertension interaction combinations. Alcohol drinkers with rs741301-AG/GG genotype also have the highest DN risk, compared to never drinkers with rs741301-AA genotype, OR (95% CI) 3.52 (1.93–4.98). Conclusions The rs741301-G allele and the rs10255208-GG genotype, gene–environment interaction between rs741301 and alcohol drinking were all associated with increased DN risk.

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Interaction Between XRCC1 Gene Polymorphisms and Obesity on Susceptibility to Papillary Thyroid Cancer in Chinese Han Population

Cellular Physiology and Biochemistry ◽

10.1159/000493027 ◽

2018 ◽

Vol 49 (2) ◽

pp. 638-644

Author(s):

Jie Zhu ◽

Ping Qi ◽

Zhenjie Li

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Haplotype Analysis ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Papillary Thyroid ◽

Xrcc1 Gene ◽

Chinese Han ◽

Hardy Weinberg Equilibrium ◽

Testing Accuracy

Background/Aims: To investigate the association of several single nucleotide polymorphisms (SNPs) within XRCC gene and additional gene- environment interaction with papillary thyroid cancer (PTC) risk. Methods: Testing for Hardy-Weinberg equilibrium in controls was conducted using SNPstats (online software: http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 5 SNPs within XRCC gene and obesity. Results: Logistic regression analysis showed that the C allele of rs861539 and T allele of rs1799782 were associated with increased PTC risk Adjusted ORs (95%CI) were 1.65 (1.23-2.12) and 1.61 (1.20-2.04). However There was no relation of rs25489 Rs25487 and rs13181 with PTC. The cross-validation consistency and the testing accuracy for each of the models were determined by GMDR analysis. One two-locus model (rs1799782 and obesity) had a testing accuracy of 62.11% Which was significant at the p < 0.01 level. The D’ value between rs1799782 and rs13181 within ERCC1 gene was more than 0.75 (0.825). So haplotype analysis was just conducted for rs1799782 and rs13181 using the SHEsis online haplotype analysis software. In all samples The haplotype C- A was observed most frequently in two groups With 49.46% and 55.79% in the PTC patients and controls Respectively. The results also indicated that haplotype T- C was significantly associated with increased PTC risk. Conclusion: The C allele of rs861539 and T allele of rs1799782 Interaction between rs1799782 and obesity and haplotype T- C were all associated with increased PTC risk.

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Pro-inflammatory cytokine polymorphisms and interactions with dietary alcohol and estrogen, risk factors for invasive breast cancer using a post genome-wide analysis for gene–gene and gene–lifestyle interaction

Scientific Reports ◽

10.1038/s41598-020-80197-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Su Yon Jung ◽

Jeanette C. Papp ◽

Eric M. Sobel ◽

Matteo Pellegrini ◽

Herbert Yu ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Visceral Obesity ◽

Cumulative Exposure ◽

Environment Interaction ◽

Dependent Manner ◽

Nucleotide Polymorphisms ◽

Genome Wide ◽

Reduction Methods

AbstractMolecular and genetic immune-related pathways connected to breast cancer and lifestyles in postmenopausal women are not fully characterized. In this study, we explored the role of pro-inflammatory cytokines such as C-reactive protein (CRP) and interleukin-6 (IL-6) in those pathways at the genome-wide level. With single-nucleotide polymorphisms (SNPs) in the biomarkers and lifestyles together, we further constructed risk profiles to improve predictability for breast cancer. Our earlier genome-wide association gene-environment interaction study used large cohort data from the Women’s Health Initiative Database for Genotypes and Phenotypes Study and identified 88 SNPs associated with CRP and IL-6. For this study, we added an additional 68 SNPs from previous GWA studies, and together with 48 selected lifestyles, evaluated for the association with breast cancer risk via a 2-stage multimodal random survival forest and generalized multifactor dimensionality reduction methods. Overall and in obesity strata (by body mass index, waist, waist-to-hip ratio, exercise, and dietary fat intake), we identified the most predictive genetic and lifestyle variables. Two SNPs (SALL1 rs10521222 and HLA-DQA1 rs9271608) and lifestyles, including alcohol intake, lifetime cumulative exposure to estrogen, and overall and visceral obesity, are the most common and strongest predictive markers for breast cancer across the analyses. The risk profile that combined those variables presented their synergistic effect on the increased breast cancer risk in a gene–lifestyle dose-dependent manner. Our study may contribute to improved predictability for breast cancer and suggest potential interventions for the women with the risk genotypes and lifestyles to reduce their breast cancer risk.

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Investigation of gene–environment interactions in relation to tic severity

Journal of Neural Transmission ◽

10.1007/s00702-021-02396-y ◽

2021 ◽

Author(s):

Mohamed Abdulkadir ◽

Dongmei Yu ◽

Lisa Osiecki ◽

Robert A. King ◽

Thomas V. Fernandez ◽

...

Keyword(s):

Tourette Syndrome ◽

Association Studies ◽

Autism Spectrum ◽

Environment Interaction ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Linear Regression Models ◽

Compulsive Disorder ◽

Gene Environment ◽

Tic Severity

AbstractTourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.

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Effects of in IL-1B/IL-1RN variants on the susceptibility to head and neck cancer in a chinese Han population

Cancer Cell International ◽

10.1186/s12935-021-01750-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yanhai Yin ◽

Fen Li ◽

Liangqian Tong ◽

Chunru Chen ◽

Bo Yuan

Keyword(s):

Logistic Regression ◽

Head And Neck Cancer ◽

Head And Neck ◽

Genetic Association ◽

Neck Cancer ◽

Chinese Han Population ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Han Population ◽

Logistic Regression Models

Abstract Background The study aimed to evaluate the relationship of IL-1B/IL-1RN polymorphisms to the predisposition of head and neck cancer (HNC) in a Chinese Han population. Methods Nine single-nucleotide polymorphisms (SNPs) in IL-1B/IL-1RN were genotyped based on Agena MassARRAY platform. Logistic regression models were used to analyze the genetic association between these SNPs and HNC risk by calculating odds ratios (ORs) and 95% confidence intervals (CI). Haplotype analysis were performed using Haploview program and logistic regression model. Results The genetic association between rs1143643 in IL-1B and the higher risk of HNC was found (OR = 1.23, 95% CI 1.04–1.46) in the overall. IL-1RN rs17042888 was related to a reduced risk of HNC in the subjects aged > 46 years (OR = 0.70, 95% CI: 0.50–0.98) and in females (OR = 0.71, 95% CI 0.52–0.98), while rs1143643 increased the predisposition of HNC among females (OR = 1.76, 95% CI 1.13–2.74). Furthermore, rs1143643 had an increased susceptibility to thyroid carcinoma (OR = 1.61, 95% CI 1.10–2.34). Moreover, compared with stage I–II, the frequency of IL-1RN rs452204-AG genotype was lower in patients with stage III–IV. Conclusions IL-1B (rs1143643) and IL-1RN (rs17042888 and rs452204) polymorphisms might be related to the individual susceptibility of HNC in the Chinese Han population. These results might help to improve the understanding of IL-1B and IL-1RN genes in the occurrence of HNC.

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Comparing Effects of FOXO3A and Residing in Urban Areas on Longevity: A Gene-Environment Interaction Study

The Journals of Gerontology Series A ◽

10.1093/gerona/glab362 ◽

2021 ◽

Author(s):

John S Ji ◽

Linxin Liu ◽

Lijing Yan ◽

Yi Zeng

Keyword(s):

Protective Effect ◽

Effect Size ◽

Urban Areas ◽

Vegetation Index ◽

Normalized Difference Vegetation Index ◽

Fine Particulate Matter ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Gene Environment Interaction ◽

Gene Environment

Abstract Forkhead box O3 (FOXO3A) is a candidate longevity gene. Urban residents are also positively associated with longer life expectancy. We conducted a gene-environment interaction to assess the synergistic effect of FOXO3A and urban/rural environments on mortality. We included 3085 older adults from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We used single nucleotide polymorphisms (SNPs) rs2253310, rs2802292, and rs4946936 to identify the FOXO3A gene and classified residential locations as "urban" and "rural." Given the open cohort design, we used the Cox-proportional hazard regression models to assess the mortality risk. We found the minor allele homozygotes of FOXO3A to have a protective effect on mortality [HR (95% CI) for rs4946936 TT vs. CC: 0.807 (0.653, 0.996); rs2802292 GG vs TT: 0.812 (0.67, 0.985); rs2253310 CC vs. GG: 0.808 (0.667, 0.978)]. Participants living in urban areas had a lower risk of mortality [HR of the urban vs. the rural: 0.854 (0.759, 0.962)]. The interaction between FOXO3A and urban and rural regions was statistically significant (pinteraction<0.01). Higher air pollution (fine particulate matter: PM2.5) and lower residential greenness (Normalized Difference Vegetation Index: NDVI) both contributed to higher mortality. After adjusting for NDVI and PM2.5, the protective effect size of FOXO3A SNPs was slightly attenuated while the protective effect size of living in an urban environment increased. The effect size of the beneficial effect of FOXO3 on mortality is roughly equivalent to that of living in urban areas. Our research findings indicate the effect of places of residence and genetic predisposition of longevity are intertwined.

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Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458509355069 ◽

2009 ◽

Vol 16 (2) ◽

pp. 133-138 ◽

Cited By ~ 88

Author(s):

K. Claire Simon ◽

Kassandra L Munger ◽

Xing Yang ◽

Alberto Ascherio

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Conditional Logistic Regression ◽

Dietary Vitamin ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Vitamin D Metabolism ◽

Logistic Regression Models ◽

Gene Environment ◽

Vitamin D Levels

The extent to which potential genetic determinants of vitamin D levels may be related to multiple sclerosis (MS) risk has not been thoroughly explored. The objective of this study was to determine whether polymorphisms in VDR, CYP27B1, CYP24A1, CYP2R1 and DBP are associated with the risk of MS and whether these variants may modify associations between environmental or dietary vitamin D on MS risk. A nested case-control study was conducted in two, large cohorts of US nurses, including 214 MS cases and 428 age-matched controls. Conditional logistic regression models were used to calculate relative risks (RR) and 95% confidence intervals (CIs) and to assess the significance of gene—environment interactions. No associations were observed for any of the single-nucleotide polymorphisms (SNPs) in VDR, CYP27B1, CYP24A1, CYP2R1 or DBP (p > 0.05 for all). The authors did observe an interaction (p = 0.04) between dietary intake of vitamin D and the vitamin D receptor FokI polymorphism on MS risk. The protective effect of increasing vitamin D was evident only in individuals with the ‘ff ’ genotype (RR = 0.2, 95% CI: 0.06, 0.78; p = 0.02 for 400 IU/day increase). It was concluded that this does not support a role for the selected SNPs involved in vitamin D metabolism in the etiology of MS. The finding of a marginally significant gene—environment interaction requires replication in larger datasets, but suggests future genetic studies may benefit from considering relevant environmental context.

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