F-box motif encoding genes as targets for the development of stress-tolerant traits in Saccharomyces cerevisiae

Stress tolerance is a useful trait actively sought by the bioprocess industry for biofactories dealing with bioconversion of varied raw materials or carbon sources. Fungal or yeast species are useful in bioconversion and are sustainable bioresources for biochemicals and biofuel production. Genetic manipulation strategies are in practice to enhance the tolerance against stress agents for the improved bioconversion process. In this review, we highlight the importance of the F-box motif encoding genes and their interactions in imparting the stress tolerance phenotype to the yeast species. The F-box motif proteins constitute a part of the SCF-E3 ligase complex and are involved in the recruitment, and ubiquitination, followed by degradation of the substrate proteins by the 26S proteasome. It highlights the current scenario on the F-box motif encoding genes and their interaction partners as targets for the stress tolerance phenotype in the yeast and plant species and their utility in the bioconversion processes.

Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring / 中国当代儿科杂志

OBJECTIVES@#To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring.@*METHODS@#A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD.@*RESULTS@#The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05).@*CONCLUSIONS@#Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.

Effects of DRD2 and 5-HTR2A gene polymorphisms and their interaction on olanzapine in the treatment of schizophrenia / 中国临床药理学与治疗学

AIM: To investigate the association of dopamine D2 receptor (DRD2) and 5-hydroxytryptamine 2A receptor (5-HTR2A) gene polymorphisms and their interactions with efficacy of olanzapine in treatment of schizophrenic patients. METHODS: A total of 147 schizophrenic patients who treated with olanzapine alone were recruited. The positive and negative symptom scale (PANSS) was used to evaluate the efficacy of drugs. According to PANSS reduction rate ≥50% and <50%, patients were divided into the effective group and the ineffective group. The gene polymorphisms of DRD2 (rs1799978, rs1800497) and 5-HTR2A (rs6311, rs6313) were detected by improved multiple ligase detection reaction (iMLDR). Multivariate Logistic regression analysis was used to analyze the correlation between genotypes and olanzapine efficacy, and multifactor dimensionality reduction (MDR) was used to analyze gene-gene interactions. RESULTS: There were significant differences in genotype and allele frequencies of rs1799978 and rs6313 between the effective group and the ineffective group (P<0.05), while there was no difference in genotype and allele frequencies of rs1800497 and rs6311 (P<0.05). Patients with GA and GG of rs1799978 locus were more effective than those with wild type AA when treated with olanzapine, and the ORs (95%CI) were 5.101 (1.118-23.267) and 6.051 (2.454-14.925), respectively. Patients with CT and CC of rs6313 locus were more effective than those with wild type TT when treated with olanzapine, and the ORs (95%CI) were 2.623 (1.054-6.528) and 3.412 (1.180-9.869), respectively. There was a interaction between the gene polymorphisms of rs1799978, rs1800497 and rs6313. The interaction model was the optimal gene-gene interaction model (P<0.05) with the verify sample accuracy rate of 0.727 3 and a cross-validation consistency of 10/10. CONCLUSION: The gene polymorphisms of DRD2 (rs1799978) and 5-HTR2A (rs6313) may be associated with efficacy of olanzapine in treatment of schizophrenic patients, and there is a interaction between DRD2 (rs1799978, rs1800497) and 5-HTR2A (rs6313) on the efficacy of olanzapine.

A review of gene-gene interaction studies in rheumatoid arthritis / 中华疾病控制杂志

To date, multiple genetic susceptible genes/loci associated with rheumatoid arthritis (RA) have been identified and confirmed through large-scale genetic association studies and genome-wide association study (GWAS). However, the heritability of RA could be not fully explained by these genetic factors, and gene-gene interaction might account for part of the missing heritability. Indeed, genetic interaction study is a critical research direction in the field of genetic epidemiology of RA, and these studies have provided novel insights into the genetic basis and pathogenesis of RA. Additionally, these studies have also provided scientific reference for risk prediction and prevention of RA. This review is aimed to present a summary of recent progress in genetic interaction study of RA, thus implicate further research in this field.

EFMDR-Fast: An Application of Empirical Fuzzy Multifactor Dimensionality Reduction for Fast Execution

Gene-gene interaction is a key factor for explaining missing heritability. Many methods have been proposed to identify gene-gene interactions. Multifactor dimensionality reduction (MDR) is a well-known method for the detection of gene-gene interactions by reduction from genotypes of single-nucleotide polymorphism combinations to a binary variable with a value of high risk or low risk. This method has been widely expanded to own a specific objective. Among those expansions, fuzzy-MDR uses the fuzzy set theory for the membership of high risk or low risk and increases the detection rates of gene-gene interactions. Fuzzy-MDR is expanded by a maximum likelihood estimator as a new membership function in empirical fuzzy MDR (EFMDR). However, EFMDR is relatively slow, because it is implemented by R script language. Therefore, in this study, we implemented EFMDR using RCPP (c++ package) for faster executions. Our implementation for faster EFMDR, called EMMDR-Fast, is about 800 times faster than EFMDR written by R script only.

HisCoM-GGI: Software for Hierarchical Structural Component Analysis of Gene-Gene Interactions

Gene-gene interaction (GGI) analysis is known to play an important role in explaining missing heritability. Many previous studies have already proposed software to analyze GGI, but most methods focus on a binary phenotype in a case-control design. In this study, we developed “Hierarchical structural CoMponent analysis of Gene-Gene Interactions” (HisCoM-GGI) software for GGI analysis with a continuous phenotype. The HisCoM-GGI method considers hierarchical structural relationships between genes and single nucleotide polymorphisms (SNPs), enabling both gene-level and SNP-level interaction analysis in a single model. Furthermore, this software accepts various types of genomic data and supports data management and multithreading to improve the efficiency of genome-wide association study data analysis. We expect that HisCoM-GGI software will provide advanced accessibility to researchers in genetic interaction studies and a more effective way to understand biological mechanisms of complex diseases.

Association of ORMDL3 and HLA-DQ single nucleotide polymorphisms in children with asthma associated Mycoplasma pneumoniae infection / 国际儿科学杂志

Objective Childhood asthma is closely related to MP infection.This study was to investigate the distribution of ORMDL3 and HLA-DQ gene SNP in children with MP-associated asthma and gene-gene interactions.Methods One hundred and ninety-four patients with MP infection were enrolled.Extraction of whole blood genomic DNA was carried out.The genotype was collected by Flnidigm Juno 96.96 Genotyping integrated fluid pathway system.The patients were divided into MP-asthma group and MP-non-asthma group.Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction.Results MP-asthma group included 63 cases (32.5％),MP-non asthma group included 131 cases (67.5％).ORMDL3 gene rs4794820 had three genotypes of AG,GG,AA.,MP-asthma group GG genotype and G allele frequency was higher than that in MP-non-asthma group.The frequency of AA genotype was the lowest among the two groups,but in the MP-non-asthma group were higher than that in the MP-asthma group.The rs7216389 had three genotypes of TT、TC、CC,the frequency of TT genotype and T allele in MP-asthma group was significantly higher than that in MP-non-asthma group.The frequency of CC genotype was the lowest among the two groups,but CC genotype in MP-non-asthma group was significantly higher than that in MP-asthma group.The rs794820 GG genotype and rs7216389 TT genotype were found to be risk factors.ORMDL3、HLA-DQA1 and HLA-DQA2 have gene-gene interaction.Conclusion MP infection is an important external cause of asthma in children.The genotype of rs7794820 GG genotype and rs7216389 TT genotype are an important internal cause of asthma after childhood MP infection.ORMDL3 rs4794820,rs7216389 and HLA-DQA1 rs9272346,HLADQA2 rs7773955 have gene-gene interaction,synergistically enhance the risk of asthma associated with asthma in children with MP.

Association study of interaction of tryptophan hydroxylase 2 with serotonin 1A receptor gene polymorphism on major depressive disorder / 中华行为医学与脑科学杂志

Objective To explore the interaction between tryptophan hydroxylase 2(TPH2) gene polymorphisms (rs4570625,rs11178997) and serotonin 1A receptor (5-HT1A) gene polymorpbisms (rs878567,rs1364043,rs6265) and the association with major depressive disorder (MDD) in a Chinese Han population.Methods The DNA isolated from peripheral blood samples of 288 MDD patients 288 healthy subjects was detected by single base primer extension assay (Snapshot).The generalized multifactor dimensionality reduction (GMDR) method was used to analyze the gene-gene interaction.Results Significant differences were found in the genotype (patients (TT:27,TA:152,AA:109),controls (TT:82,TA:105,AA:101),P＜0.01) and allele(patients (T:206,A:370),controls (T:269,A:307),P＜0.01) frequencies of rs1 1178997 within TPH2 between MDD patients and controls.Statistically,a greater risk of developing MDD was found in individuals with an rs1 1178997 A-allele(OR=1.574,95％CI=1.243-1.993).The interaction between TPH2 (rs4570625,rs1 1178997) and 5-HT1A (rs878567,rs1364043,rs6265) was considered as the best multi-locus model,and this showed a testing accuracy of 57.67％ and a CV consistency of 10/10.And this interaction had a significant effect on the risk of MDD (P=0.0107).Conclusion There may be an association between the interaction of TPH2 and 5-HT1A polymorphisms and MDD.

Gene-gene interactions of suicidal behavior by multifactor dimensionality reduction analysis :Do both 5-HT and GAD1 work? / 西安交通大学学报(医学版)

Objective To investigate gene-gene interactions of suicidal behavior with single-nucleotide-polymorphism (SNP) in MAOA ,GAD1 and 5-HTR2C by multifactor dimensionality reduction .Methods For this case-control study ,six SNPs were captured in related genes and detected in blood samples obtained from 21 patients with suicidal behavior and 50 healthy individuals .The genotype frequency and allele frequency as well as the Hardy-Weinberg equilibrium (HWE) ,tests were performed and compared by plink software .The gene-gene interactions models were built by the MDR software .Results The HWE test for case group showed that rs3813928 rs518147 of 5-HTR2C gene was not in line with HWE ( P< 0 .05) .However ,the additive model analysis after adjustment by gender indicated that the polymorphism had a positive correlation with suicidal behavior in case group .The case and control groups differed significantly only in genotype frequencies of 5-HTR2C gene (χ2 =6 .18 , P=0 .04) .There was no significant difference in allele and genotype frequencies of the other genes ( P>0 .05) .The best combination model of MDR was rs5953210-rs769391 OR=20 .19 ,95% CI 4 .19-97 .38 , P<0 .01 ,with significant interaction . Conclusion The 5-HTR2C gene rs3813928 and rs518147 polymorphisms may play an important role in the susceptibility to suicidal behavior .The combination of MAOA with GAD1 has a significant interaction which may increase the risk of suicidal behavior .

ITPKC and SLC11A1 Gene Polymorphisms and Gene-Gene Interactions in Korean Patients with Kawasaki Disease

PURPOSE: Kawasaki disease (KD) is an acute systemic vasculitis. Both the etiology of KD and the erythema of Bacille Calmette-Guérin (BCG) injection sites observed in the disease are poorly understood. We investigated the association between KD and single nucleotide polymorphisms (SNPs) in two candidate genes: inositol 1,4,5-triphosphate 3-kinase (ITPKC), a well-studied KD-associated gene, and solute carrier 11a1 (SLC11A1), which is associated with the hypersensitive reaction to the BCG strain in Koreans. MATERIALS AND METHODS: Associations between KD and SNPs in two genes were evaluated. Potential associations between BCG injection site erythema and SNPs in two genes were also evaluated. Gene-gene interactions between ITPKC and SLC11A1 in KD and BCG injection site erythema were also analyzed. RESULTS: Three tagging SNPs in ITPKC and five tagging SNPs in SLC11A1 were genotyped in 299 KD patients and 210 control children. SNP rs28493229 in ITPKC was associated with KD and coronary artery complications. SNP rs77624405 in SLC11A1 was associated with KD. Comparisons of KD patients with and without BCG injection site erythema revealed that SNP rs17235409 in SLC11A1 was associated with erythema; no erythema-associated SNPs in ITPKC were identified. Interactions between ITPKC rs28493229_GG and SLC11A1 rs17235409_GA and between ITPKC rs10420685_GG and SLC11A1 rs17235409_AA were strongly associated with BCG injection site erythema. CONCLUSION: This study identified several important polymorphisms in the ITPKC and SLC11A1 genes in Koreans. The genetic variants identified in this study affected KD and erythema of BCG injection sites independently and through gene-gene interactions. Also, the effects of the polymorphisms were age-dependent.

Gene-gene interaction on central obesity in school-aged children in China / 中华流行病学杂志

Objective To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China.Methods A total of 3502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected,and based on the age and sex specific waist circumference (WC) standards in the BCAMS study,1196 central obese cases and 2306 controls were identified.Genomic DNA was extracted from peripheral blood white cells using the salt fractionation method.A total of 6 single nucleotide polymorphisms (FTO rs9939609,MC4R rs17782313,BDNF rs6265,PCSK1 rs6235,SH2B1 rs4788102,and CSK rs1378942) were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems,Foster City,CA,USA).Logistic regression model was used to investigate the association between 6 SNPs and central obesity.Gene-gene interactions among 6 polymorphic loci were analyzed by using the Generalized Multifactor Dimensionality Reduction (GMDR) method,and then logistic regression model was constructed to confirm the best combination of loci identified in the GMDR.Results After adjusting gender,age,Tanner stage,physical activity and family history of obesity,the FTO rs9939609-A,MC4Rrs 17782313-C and BDNF rs6265-G alleles were associated with central obesity under additive genetic model (OR=1.24,95％CI:1.06-1.45,P=0.008;OR=1.26,95％CI:1.11-1.43,P=2.98 × 10-4;OR=1.18,95％ CI:1.06-1.32,P=0.003).GMDR analysis showed a significant gene-gene interaction between MC4R rs17782313 and BDNF rs6265 (P=0.001).The best two-locus combination showed the cross-validation consistency of 10/10 and testing accuracy of 0.539.This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated.Moreover,the combination of MC4R rs17782313-C and BDNF rs6265-G was associated with an increased risk of central obesity after adjustment for gender,age,Tanner stage,physical activity and family history of obesity.Conclusions Our study showed that FTO rs9939609-A,MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity,and statistical interaction between MC4R rs17782313-C and BDNF rs6265-G increased risk of central obesity in school-aged children in China.

Gene-gene interaction on central obesity in school-aged children in China / 中华流行病学杂志

Objective To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China.Methods A total of 3502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected,and based on the age and sex specific waist circumference (WC) standards in the BCAMS study,1196 central obese cases and 2306 controls were identified.Genomic DNA was extracted from peripheral blood white cells using the salt fractionation method.A total of 6 single nucleotide polymorphisms (FTO rs9939609,MC4R rs17782313,BDNF rs6265,PCSK1 rs6235,SH2B1 rs4788102,and CSK rs1378942) were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems,Foster City,CA,USA).Logistic regression model was used to investigate the association between 6 SNPs and central obesity.Gene-gene interactions among 6 polymorphic loci were analyzed by using the Generalized Multifactor Dimensionality Reduction (GMDR) method,and then logistic regression model was constructed to confirm the best combination of loci identified in the GMDR.Results After adjusting gender,age,Tanner stage,physical activity and family history of obesity,the FTO rs9939609-A,MC4Rrs 17782313-C and BDNF rs6265-G alleles were associated with central obesity under additive genetic model (OR=1.24,95％CI:1.06-1.45,P=0.008;OR=1.26,95％CI:1.11-1.43,P=2.98 × 10-4;OR=1.18,95％ CI:1.06-1.32,P=0.003).GMDR analysis showed a significant gene-gene interaction between MC4R rs17782313 and BDNF rs6265 (P=0.001).The best two-locus combination showed the cross-validation consistency of 10/10 and testing accuracy of 0.539.This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated.Moreover,the combination of MC4R rs17782313-C and BDNF rs6265-G was associated with an increased risk of central obesity after adjustment for gender,age,Tanner stage,physical activity and family history of obesity.Conclusions Our study showed that FTO rs9939609-A,MC4R rs17782313-C and BDNF rs6265-G alleles were associated with central obesity,and statistical interaction between MC4R rs17782313-C and BDNF rs6265-G increased risk of central obesity in school-aged children in China.

Microsomal epoxide hydrolase gene polymorphisms and susceptibility to prostate cancer: A systematic review.

Microsomal epoxide hydrolase (mEH) is a crucial biotransformation enzyme that has capability to metabolize a large number of structurally divergent, highly reactive epoxides, and numerous environmentally exposed carcinogens. It catalyzes the conversion of xenobiotic epoxide compounds into more polar diol metabolites and may play important part of the enzymatic defense against adverse effects of foreign compounds. Most commonly, two functional polymorphisms affecting mEH enzyme activity have been identified: One in exon 3 and other in exon 4 of the mEH gene, which results in His113Tyr and Arg139His amino acid substitutions, respectively. Recent reports have shown that polymorphisms in mEH gene loci may an important risk factor for susceptibility of prostate cancers (PCs), worldwide, but inconsistent finding were also be illustrated. To the best of our knowledge, globally, there is no any systematic review has been published related to mEH gene polymorphisms and PC risk. Thus, in the current review, we have discussed the association between mEH gene polymorphisms, gene–environmental interaction, and PC risk.

Exploring mechanisms of Panax notoginseng saponins in treating coronary heart disease by integrating gene interaction network and functional enrichment analysis / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the mechanisms of Panax notoginseng saponins (PNS) in treating coronary heart disease (CHD) by integrating gene interaction network and functional enrichment analysis.</p><p><b>METHODS</b>Text mining was used to get CHD and PNS associated genes. Gene-gene interaction networks of CHD and PNS were built by the GeneMANIA Cytoscape plugin. Advanced Network Merge Cytoscape plugin was used to analyze the two networks. Their functions were analyzed by gene functional enrichment analysis via DAVID Bioinformatics. Joint subnetwork of CHD network and PNS network was identifified by network analysis.</p><p><b>RESULTS</b>The 11 genes of the joint subnetwork were the direct targets of PNS in CHD network and enriched in cytokine-cytokine receptor interaction pathway. PNS could affect other 85 genes by the gene-gene interaction of joint subnetwork and these genes were enriched in other 7 pathways. The direct mechanisms of PNS in treating CHD by targeting cytokines to relieve the inflflammation and the indirect mechanisms of PNS in treating CHD by affecting other 7 pathways through the interaction of joint subnetwork of PNS and CHD network. The genes in the 7 pathways could be potential targets for the immunologic adjuvant, anticoagulant, hypolipidemic, anti-platelet and anti-hypertrophic activities of PNS.</p><p><b>CONCLUSIONS</b>The key mechanisms of PNS in treating CHD could be anticoagulant and hypolipidemic which are indicated by analyzing biological functions of hubs in the merged network.</p>

Efficient Strategy to Identify Gene-Gene Interactions and Its Application to Type 2 Diabetes

Over the past decade, the detection of gene-gene interactions has become more and more popular in the field of genome-wide association studies (GWASs). The goal of the GWAS is to identify genetic susceptibility to complex diseases by assaying and analyzing hundreds of thousands of single-nucleotide polymorphisms. However, such tests are computationally demanding and methodologically challenging. Recently, a simple but powerful method, named “BOolean Operation-based Screening and Testing” (BOOST), was proposed for genome-wide gene-gene interaction analyses. BOOST was designed with a Boolean representation of genotype data and is approximately equivalent to the log-linear model. It is extremely fast, and genome-wide gene-gene interaction analyses can be completed within a few hours. However, BOOST can not adjust for covariate effects, and its type-1 error control is not correct. Thus, we considered two-step approaches for gene-gene interaction analyses. First, we selected gene-gene interactions with BOOST and applied logistic regression with covariate adjustments to select gene-gene interactions. We applied the two-step approach to type 2 diabetes (T2D) in the Korea Association Resource (KARE) cohort and identified some promising pairs of single-nucleotide polymorphisms associated with T2D.

Gene-Gene Interaction Analysis for the Accelerated Failure Time Model Using a Unified Model-Based Multifactor Dimensionality Reduction Method

Although a large number of genetic variants have been identified to be associated with common diseases through genome-wide association studies, there still exits limitations in explaining the missing heritability. One approach to solving this missing heritability problem is to investigate gene-gene interactions, rather than a single-locus approach. For gene-gene interaction analysis, the multifactor dimensionality reduction (MDR) method has been widely applied, since the constructive induction algorithm of MDR efficiently reduces high-order dimensions into one dimension by classifying multi-level genotypes into high- and low-risk groups. The MDR method has been extended to various phenotypes and has been improved to provide a significance test for gene-gene interactions. In this paper, we propose a simple method, called accelerated failure time (AFT) UM-MDR, in which the idea of a unified model-based MDR is extended to the survival phenotype by incorporating AFT-MDR into the classification step. The proposed AFT UM-MDR method is compared with AFT-MDR through simulation studies, and a short discussion is given.

Genetic Association Analysis of Fasting and 1- and 2-Hour Glucose Tolerance Test Data Using a Generalized Index of Dissimilarity Measure for the Korean Population

Glucose tolerance tests have been devised to determine the speed of blood glucose clearance. Diabetes is often tested with the standard oral glucose tolerance test (OGTT), along with fasting glucose level. However, no single test may be sufficient for the diagnosis, and the World Health Organization (WHO)/International Diabetes Federation (IDF) has suggested composite criteria. Accordingly, a single multi-class trait was constructed with three of the fasting phenotypes and 1- and 2-hour OGTT phenotypes from the Korean Association Resource (KARE) project, and the genetic association was investigated. All of the 18 possible combinations made out of the 3 sets of classification for the individual phenotypes were taken into our analysis. These were possible due to a method that was recently developed by us for estimating genomic associations using a generalized index of dissimilarity. Eight single-nucleotide polymorphisms (SNPs) that were found to have the strongest main effect are reported with the corresponding genes. Four of them conform to previous reports, located in the CDKAL1 gene, while the other 4 SNPs are new findings. Two-order interacting SNP pairs of are also presented. One pair (rs2328549 and rs6486740) has a prominent association, where the two single-nucleotide polymorphism locations are CDKAL1 and GLT1D1. The latter has not been found to have a strong main effect. New findings may result from the proper construction and analysis of a composite trait.

Mining Alzheimer's Disease Susceptible Genes Based on Data Integration Strategy / 中国康复理论与实践

@# Objective To clarify the role of the known genes and new discovered genes, which were important to the pathogenesis of Alzheimer's disease (AD), in order to provide targets for clinical prevention, diagnosis and treatment. Methods In order to predict AD susceptible genes, the website databases (OMIM, AlzGene) and a variety of pathogenic gene prediction tools such as Endeavour, Gene Prospector, GLAD4U and ProphNet were used to make biological analysis. Results Disease-causing genes were directly obtained from the OMIM and Alzgene databases, and related genes were collected by 4 kinds of tools (select gene whose frequency was 3 or more). The data were shared and a list of 25 genes was gotten. These genes were CALHM1、 ABCA7、 A2M、 CLU、 SORL1、 HFE、 CD2AP、 APP、 ACE、 PICALM、 APOE、 NOS3、 MS4A6A、 PLD3、 CR1、 ADAM10、 MS4A4E、 BLMH、 PSEN1、 CD33、 PSEN2、 MPO、 APBB2、 BIN1 and PLAU. Conclusion CALHM1, ABCA7, A2M and CLU, etc., have a certain correlation with AD, which provide theoretical basis for further research of AD genics and clinical treatment.

Joint action of CXCL16 and TNF-α genes polymorphisms in patients with atherosclerotic cerebral infarction / 实用医学杂志

Objective To investigate the joint action of CXCL16 G1850A and TNF-α T1031C genes polymorphisms in patients with atherosclerotic cerebral infarction (ACI). Methods CXCL16 gene, G1850A and TNF-α gene T1031C mononucleotide polymorphism were tested with polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) in 120 ACI patients and 75 healthy controls. Results The CXCL16 gene 1850 site AA genotype (35.8% vs 20.0%), A allele frequency (59.6% vs 44.0%), the TNF-αgene 1031 site CC genotype(2.5% vs 1.3%), C allele frequency(21.3% vs 11.3%)in ACI group were significantly higher than in the control group(P < 0.05). There was a positive correlation between the joint action of CXCL16 G1850A and TNF-α T1031C genes polymorphisms and ACI (χ2= 7.502,df = 2,P = 0.023). Conclusion The CXCL16 gene 1850, A allele and TNF-α gene 1031 C allele were risk factors for ACI. There is a positive correlation between the joint action of CXCL16 G1850A and TNF-α T1031C genes polymorphisms on ACI.

Effect of DRD1, DRD3 gene knockout and double gene knockout on body weight in mice / 中国比较医学杂志

Objective To study the effect of dopamine receptors on neurological and physiological activities. Methods Dopamine D1 receptor gene (DRD1) knockout mice and dopamine D3 receptor (DRD3) gene knockout mice were introduced, and double gene knockout mice were bred in our lab.Seven SPF male mice in each group were used in this experiment.The food intake, water intake, body weight gain for 24 hours were tested on the age of 30 d, 50 d, and 70 d and were compared with those of wild type mice.Results DRD1 gene and DRD3 gene showed significant effect on the body weight in mice in age of 21 day and 35 day, but at the age of 90 day, the differences became insignificant among the mice of various genetypes.Conclusions Dopamine may effect on the foraging and satiety in newborn mice through regulating the hypothalamic-pituitary-adrenal ( HPA ) axis activity, and finally leads to a reduced body weight gain in newborn mice and puppies during lactation.Furthermore, DRD1 gene and DRD3 gene may influence on body weight of newborn mice through regulating mothers’ lactation, lead to a lower body weight at ablactation, and compensatory increase of body weight after ablactation.Our results provide a substantial foundation for studying the function and interaction of DRD1 and DRD3 genes.