Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

Evaluating the scope of human leukocyte antigen polymorphisms influencing hepatitis B virus-related liver cancer and cirrhosis through multi-clustering analysis

Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease progression.Nguyen et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering analysis.Here,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.

CYP4F2 polymorphism as a genetic risk factor for major hemorrhagic complications in Chinese patients on warfarin therapy

Warfarin is a commonly used anticoagulant with a narrow therapeutic range and risk of hemorrhagic complications. After CYP2C9 and VKORC1, CYP4F2 was confirmed as the third principle genetic determinant of warfarin dose variability.

Genetic polymorphisms predict response to anti-tumor necrosis factor treatment in Crohn's disease

To investigate genetic factors that might help define which Crohn’s disease (CD) patients are likely to benefit from anti-tumor necrosis factor (TNF) therapy. METHODSThis was a prospective cohort study. Patients were recruited from a university digestive disease practice database. We included CD patients who received anti-TNF therapy, had available medical records (with information on treatment duration and efficacy) and who consented to participation. Patients with allergic reactions were excluded. Patients were grouped as ever-responders or non-responders. Genomic DNA was extracted from peripheral blood, and 7 single nucleotide polymorphisms (SNPs) were assessed. The main outcome measure (following exposure to the drug) was response to therapy. The patient genotypes were assessed as the predictors of outcome. Possible confounders and effect modifiers included age, gender, race, and socioeconomic status disease, as well as disease characteristics (such as Montreal criteria). RESULTS121 patients were included. Twenty-one were non-responders, and 100 were ever-responders. Fas ligand SNP (rs763110) genotype frequencies, TNF gene -308 SNP (rs1800629) genotype frequencies, and their combination, were significantly different between groups on multivariable analysis controlling for Montreal disease behavior and perianal disease. The odds of a patient with a Fas ligand CC genotype being a non-responder were four-fold higher as compared to a TC or TT genotype (P = 0.009, OR = 4.30, 95%CI: 1.45-12.80). The presence of the A (minor) TNF gene -308 allele correlated with three-fold higher odds of being a non-responder (P = 0.049, OR = 2.88, 95%CI: 1.01-8.22). Patients with the combination of the Fas ligand CC genotype and the TNF -308 A allele had nearly five-fold higher odds of being a non-responder (P = 0.015, OR = 4.76, 95%CI: 1.35-16.77). No difference was seen for the remaining SNPs. CONCLUSIONThe Fas-ligand SNP and TNF gene -308 SNP are associated with anti-TNF treatment response in CD and may help select patients likely to benefit from therapy.

Genetic polymorphism of CYP2A6 is one of the potential factors determining tobacco-related cancer risk

While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.

Genetic Predisposition for Type 2 Diabetes Mellitus in a Cameroonian Population: Contribution of rs4731702 (C/T) Polymorphism of Krüppel-Like Factor 14 Gene

Introduction: Krüppel Like Factor 14 (KLF14) gene has recently been identified as a master gene for multiple metabolic phenotypes. The aim of the research study was to investigate the relationship between KLF14 rs4731702 (C/T) gene polymorphism with Type 2 Diabetes Mellitus (T2DM) in a Cameroonian population. Patients and Methods: This case-control study was conducted in 85 patients with T2DM and 95 healthy normoglycemic controls. All were nonrelated, of Cameroonian origin, and were adults aged 24 years old and above. Demographic, clinical and biological data were collected, and biochemical explorations were performed using enzymatic colorimetric methods. The genotyping of KLF14 rs4731702 (CT) gene polymorphism was done by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. Results: In comparing the Cameroonian population that consisted of 85 patients with T2DM and 95 healthy controls, the minor or risk allele of the rs4731702 (C/T) polymorphism of the KLF14 gene was T (63.53% diabetic patients vs. 26.32% healthy controls, OR = 4.877 and p < 0.0001) while the protective allele was C (36.47% diabetic patients vs. 73.68% healthy controls, OR = 0.205 and p < 0.0001). The susceptibility to T2DM was higher among subjects having the CT and TT genotypes with OR = 2.721 and p = 0.0145) and OR = 3.907 and p < 0.0001) respectively. This gene polymorphism was not preferentially associated with a specific diabetes phenotype. Conclusion: This study has demonstrated for the first time the relationship between the KLF14 rs4731702 (C/T) gene polymorphism and T2DM in this Cameroonian population. This gene polymorphism could be a promising target for personalized medicine through the development of clinical genetic testing.

Genetic Polymorphism of Eighteen Lycium barbarum Resources Based on nrDNA ITS Sequence

[Objective] The study aimed to investigate the genetic polymorphism of eighteen Lycium barbarum resources via nrDNA ITS sequencing. [Method] The genomic DNAs from Lycium barbarum leaves were isolated by modified CTAB method for PCR amplification on the nrDNA ITS region using specifically synthesized primers; the amplified fragments were cloned and sequenced, then the sequencing results were clustered. [Result] nrDNA ITS sequences of the tested eighteen Lycium barbarum were firstly obtained in the present study. For all eighteen tested materials, the variation range of whole ITS region was 559-634 bp, with an average of 612 bp; alignment analyses showed that the whole length of internal transcribed spacer (ITS1+ITS2) was 480 bp, within which there are 194 variation sites (accounting for 40.4%) and 286 conserved sites (accounting for 59.6%). The cluster results showed that the eighteen tested materials could be grouped into three classes. [Conclusion] Analysis of nrDNA ITS sequence may avail to identify the Lycium barbarum germplasm resources.

Characterization of Genetic Polymorphism of Novel MHC B-LBⅡ Alleles in Chinese Indigenous Chickens

Genetic polymorphism of the major histocompatibility complex （MHC） B-LBⅡ gene was studied by amplification of exon 2 using PCR, followed by cloning and DNA sequencing in eight indigenous Chinese chicken populations. To reveal the genetic variation of the B-LB Ⅱ gene, 37 types of patterns detected by PCR-SSCP were investigated first, which would be used to screen novel B-LB Ⅱsequences within the breeds. The types of PCR-SSCP patterns and final sequencing allowed for the identification of 31 novel MHC B-LBⅡ alleles from 30 unrelated individuals of Chinese chickens that were sampled. These are the first designators for the alleles of chicken MHC B-LBⅡ gene based on the rule of assignment for novel mammalian alleles. Sequence alignment of the 31 B-LB Ⅱ alleles revealed a total of 68 variable sites in the fragment of exon 2, of which 51 parsimony informative and 17 singleton variable sites were observed. Among the polymorphic sites, the nucleotide substitutions in the first and second positions of the codons accounted for 36.76% and 35.29%, respectively. The sequence similarities between the alleles were estimated to be 90.6%-99.5%. The relative frequencies of synonymous and nonsynonymous nucleotide substitutions within the region were 2.92%±0.94% and 14.64%±2.67%, respectively. These results indicated that the genetic variation within exon 2 appeared to have largely arisen by gene recombination and balancing selection. Alignment of the deduced amino acid sequences of the β1 domain coded by exon 2 revealed 6 synonymous mutations and 27 nonsynonymous substitutions at the 33 disparate sites. In particular, the nonsynonymous substitutions at the putative peptide-binding sites are considered to be associated with immunological specificity of MHC B-LB Ⅱ molecule in Chinese native chickens. These results can provide a molecular biological basis for the study of disease resistance in chicken breeding.

Genetic Polymorphism of Wheat by IRAP Analysis Based on Retrotransposon Wis2-1 A

[Objective] To analyze genetic polymorphism of different species of wheat. [Method] The DNA of young seedlings from 21 species of wheat was isolated,and their genetic polymorphism was analyzed by inter-retrotransposon amplified polymorphism （IRAP） using a molecule marker technology based on wheat retrotransposon Wis2-1 A. [Result] As shown by clustering map of the electrophoresis results,19 species of wheat assembled as cluster with different genetic distance. Most of the wheat species were distinguished. The genetic polymorphism among different species of wheat could be evaluated by this method objectively. [Conclusion] The analysis of IRAP based on wheat retrotransposon Wis2-1A could give a basis for breeding of wheat.

A Novel Genetic Polymorphism and Its Genetic Effects of Porcine Heart Fatty Acid-Binding(H-FABP)Gene in Intron 1

[Objective] The aim was to provide basic reference for the use of H-FABP gene in marker-assisted selection of the breeding process of pig.[Method] Single-nucleotide polymorphisms of the H-FABP gene in Shanxi White pig,Mashen pig,Large White pig,Landrace and Duroc were tested by PCR-SSCP,and the correlation between genotype and intramuscular fat content in pigs were analyzed.[Result] One polymorphism was found in the amplified region of intron 1 of porcine H-FABP gene,in which two alleles（A and B）and three genotypes（AA,AB,and BB）were examined.C→T transition was detected by sequencing the homozygotes.The multiple comparison of the distribution of genotype in different pig varieties revealed that Mashen pig showed extremely significant difference（P0.01）in genotype distribution with Shanxi White,Landrace,Large White and Duroc breeds;whereas no significant differences（P0.05）were found in genotype distribution between other breeds.Based on the fixed effect model,extremely significant differences（P 0.01）were found in the intramuscular fat content among different H-FABP genotypes.Using least square analysis,it was found that there was significant differences（P 0.05）in the intramuscular fat content between the individuals of the BB genotypes and those of the AA genotypes.[Conclusion] The H-FABP genotype had significant effects on the meat quality.

Genetic Polymorphism of Ten Microsatellites in Two Goat Breeds and Its Relationship with Heterosis

[Objective] This study aimed to investigate the genetic diversity of Macheng black goat and its correlation with heterosis.[Method] Ten microsatellite markers were selected for polymorphism investigation and statistical analysis of Boer goat and Macheng black goat populations.[Result] The results showed that totally 175 alleles were found in 10 microsatellite loci; to be specific,the maximum number of detected alleles was 23,and the minimum number was 10; the effective number of alleles （Ne） was 6.4-18.1,with absolute difference value of 1.6-8.1 from the observed number of alleles.The highest gene frequency was 0.239 1 and the lowest was 0.002 7.The polymorphic information contents of all the ten microsatellite markers were above 0.95.The observed heterozygosity （Ho） ranged from 0.616 7 to 0.984 4 and the expected heterozygosity （He） ranged from 0.844 1 to 0.944 6.The average expected heterozygosity of Boer goat and Macheng black goat was respectively 0.894 0 and 0.906 7.Various body weight and body size indices of Boer goatxMacheng black goat hybrids were improved in varying degrees compared with Macheng black goat （with an increase range of 0.32％-30.06％）.The average heterosis rates of body height and chest girth were relatively high,while average heterosis rate of body weight was relatively low.[Conclusion] The genetic distance between Boer goat and Macheng black goat was 0.379 5,which is consistent with the geographical distribution of Boer goat and Macheng black goat populations and is fully relevant to the heterosis of Boer goat × Macheng black goat hybrids,indicating that investigating polymorphism via microsatellite loci is one of the feasible means to predict and analyze heterosis between varieties.

Studies on Genetic Polymorphism of Different Biotypeswith RAPD Analysis1

In the present paper, RAPD was used to study the genetic polymorphism of fisheswith different genome combinations. Our results indicated that four of the 26 random primersproduced distinct and reproducible electrophoretic patterns which were genome-specific andcould distinguish different biotypes. This enabled us to derive a diagnostic profile, from whichwe constructed a molecular marker key for different biotypes. By the analysis of the data ofRAPD patterns, the genetic relationship was constructed with UPGMA (unweighted pair-groupmethod with arithmetical averages). Our experiments also concluded that RAPD was moresuccessful in variety identification than protein polymorphism analysis and serohematology for itstechnological simplicity and sensitivity.

Fibroblast growth factor receptor 4 Gly388Arg polymorphism in Chinese gastric cancer patients

AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 ageand sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ 2 test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ 2 test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ 2 = 3.589, P = 0.166) and alleles (χ 2 = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ 2 = 5.449, P = 0.020), well differentiated (log rank χ 2 = 12.798, P = 0.000), T1 or T2 stage (log rank χ 2 = 4.745, P = 0.029), without lymph node involvement (log rank χ 2 = 6.647, P = 0.010), and at an early clinical stage (log rank χ 2 = 4.615, P = 0.032). CONCLUSION: Our results suggest that the FGFR4 Gly388Arg polymorphism is not a risk factor for GC cancer initiation but that it is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or at an early clinical stage.

Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients

Glutathione S-transferases （GSTs）, superoxide dismutase 2 （SOD2） and NAD（P）H：quinone oxidoreductase 1 （NQO1） are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase 7：1 （GSTT1）-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction （PCR）. Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism （PCR-RFLP） method. A significantly better response to varicocelectomy was found in patients with the GSTTI-wt genotype （63.2%） and NQO1-Ser/Ser genotype （80.0%） than in those with GSTTI-null genotype （35.3%） and NQO1-Pro/Pro or NQO1- Pro/Ser genotype （45.2%）, respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.

Role of polymorphisms in genes that encode cytokines and Helicobacter pylori virulence factors in gastric carcinogenesis

The Helicobacter pylori(H. pylori) infection is a determinant factor in gastric cancer(GC) development. However, the infection outcomes are variable and depend on both host and bacterial characteristics. Some host cytokines such as interleukin(IL)-1β, IL-1 Ra, IL-8, IL-10 and tumor necrosis factor-α play important roles in the host immune system response to the pathogen, in the development of gastric mucosal lesions and in cell malignant transformation. Therefore, these host factors are crucial in neoplastic processes. Certain polymorphisms in genes that encode these cytokines have been associated with an increased risk of GC. On the other hand, various virulence factors found in distinct H. pylori bacterial strains, including cytotoxinassociated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and blood group antigen binding adhesin, have been associated with the pathogenesis of different gastric diseases. The virulent factors mentioned above allow the successful infection by the bacterium and play crucial roles in gastric mucosa lesions, including malignant transformation. Moreover, the role of host polymorphisms and bacterial virulence factors in gastric carcinogenesis seems to vary among different countries and populations. The identification of host and bacterium factors that are associated with an increased risk of GC development may be useful in determining the prognosis of infection in patients, what could help in clinical decision-making and in providing of an optimized clinical approach.

hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer

AIM:To determine the association of hOGG1 (8-oxoguanine glycosylase I,OGG1) polymorphism of Ser326Cys substitution with colon cancer risk and possible interaction with known environmental risk factors. METHODS:A case-control study with 125 colon cancer cases and 247 controls was conducted, RESULTS:There was no major difference in Ser326Cys genotype distribution between cases and controls.The meat intake tended to increase the odds ratio for colon cancer with an OR of 1.72 (95 % confidence interval;CI=1.12-2.76). Such tendency was more prominent in Cys/Cys carriers (OR=4.31,95 % CI=1.64-11.48),but meat intake was not a significant risk factor for colon cancer in Ser/Ser or Ser/ Cys carriers.The OR for colon cancer was elevated with marginal significance in smokers who were Cys/Cys carriers (OR=2.75,95 % CI=1.07-7.53) but not in Ser/Ser or Ser/ Cys carriers. CONCLUSION:These results suggest that the hOGG1 Ser326Cys polymorphism is probably not a major contributor to individual colon cancer susceptibility overall,but the Cys/ Cys genotype may alter the impact of some environmental factors on colon cancer development.

Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: An association study in New Zealand Caucasians and meta-analysis

AIM:To investigate the association of macrophage migration inhibitory factor(MIF)promoter polymorphisms with inflammatory bowel disease(IBD)risk.METHODS:One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP-173G>C(rs755622)and the repeat polymorphism CATT5-8(rs5844572)using a predesigned TaqMan SNP assay and capillary electrophoresis,respectively.Data were analysed for single site and haplotype association with IBD risk and phenotype.Meta-analysis was employed,to assess cumulative evidence of association of MIF-173G>C with IBD.All published genotype data for MIF-173G>C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies.Imputed genotypes for MIF-173G>C were generated from the Wellcome Trust Case Control Consortium(and National Institute of Diabetes and Digestive and Kidney Diseases).Separate meta-analyses were performed on Caucasian Crohn’s disease(CD)(3863 patients,6031controls),Caucasian ulcerative colitis(UC)(1260 patients,1987 controls),and East Asian UC(416 patients and 789 controls)datasets using the Mantel-Haenszel method.The New Zealand dataset had 93%power,and the meta-analyses had 100%power to detect an effect size of OR=1.40 atα=0.05,respectively.RESULTS:In our New Zealand dataset,single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD,UC,and IBD or disease phenotype(all P values>0.05).Haplotype analysis found the CATT5/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients(0.6 vs 0.01;P=0.03,OR=0.22;95%CI:0.05-0.99),but this association did not survive bonferroni correction.Meta-analysis of our New Zealand MIF-173G>C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD,UC,or overall IBD.Similarly,meta-analysis of all published MIF-173G>C data from East Asian datasets(416UC patients,789 controls)found no association of this promoter polymorphism with UC.

Interaction of methylenetetrahydrofolate reductase C677T,cytochrome P4502E1 polymorphism and environment factors in esophageal cancer in Kazakh population

AIM： To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase （MTHER） and cytochrome P4502E1 （CY- P4502E1）, environment risk factors with esophageal cancer （EC） in Kazakh, a high EC incidence area of Xinjiang Uygur Autonomous Region, China. METHODS： A 1：2 matched case-control study was conducted with 120 cases of EC and 240 populationor hospital-based controls. The controls were matched for sex, nationality, area of residence and age within a 5-year difference. MTHER and CYP4502E1 genotypes were identified by PCR-based restriction fragment length polymorphism （RFLP）. A conditional logistic regression model was established to identify risk factors. The strata method was adopted in interaction analysis. RESULTS： Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water （shallow well, or river） were found to be the risk factors for EC. Individuals with the MTHFR677 （C/T ＋ T/T） genotype had a 2.62-fold （95% CI： 1.61-4.28） risk of developing EC compared with those who carried the C/C genotype. Individuals with the CYP4502EIC1/C1 genotype had a 3.00-fold （95% CI： 1.82-4.96） risk compared with those who carried the CYP4502E1 （C1/C2 ＋ C2/C2） genotype. Gene-environment interaction analysis showed that MTHFR677 gene polymorphism was correlated with consumption of green vegetables and fresh fruit, while CYP4502E1 C1/C1 was correlated with alcohol drinking and unsafe drinking water. MTHFR and CYP4502E1 analysis of gene-gene interaction showed that individuals with the MTHFR677 （C/T ＋ T/T） and CYP4502EIC1/ C1 genotypes had a 7.41-fold （95% CI： 3.60-15.25） risk of developing EC compared with those who carried the MTHFR677C/C and CYP4502E1 RsaI C1/C2 ＋ C2/C2 genes, and the interaction rate was higher than that of the two factors alone. CONCLUSION： Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water （shallow well, or river） and polymorphisms in MTHFR and CYP4502E1 genes are important risk factors for EC. There is a synergistic interaction among polymorphisms in MTHFR and CYP4502E1 genes and environment factors. MTHFR and CYP4502E1 genes can be used as biomarkers for prevention of EC in Kazakh, Xinjiang Uygur Autonomous Region, China.

Porcine growth differentiation factor 9 gene polymorphisms and their associations with litter size

Growth differentiation factor 9 （GDF9） is expressed in oocytes and is thought to be required for ovarian folliculogenesis. Given this function, GDF9 may be considered as a candidate gene controlling pig ovulate rate. In this study, the complete coding sequence was cloned （encoding a 444 amino acid）, intron sequence and partial 5＇-UTR of pig GDF9. RT-PCR results showed that GDF9 mRNA is expressed in a wide range of tissues of the ruttish Erhualian pig. The expression levels of GDF9 mRNA in pituitary, ovary, uterus and oviduct are higher in the Erhualian pigs than those in Duroc pigs, especially in pituitary with a significant difference （P 〈 0.05）. Comparative sequencing revealed 12 polymorphisms, including 8 single nucleotide polymorphisms （SNPs） and one 314 bp indel in noncoding regions, and the other 3 SNPs in coding regions. Four polymorphisms, G359C, C1801T, T1806C and 314 bp indel, were developed as markers for further use in population variation and association studies. The G359C polymorphism segregates only in Chinese native pigs, Erhualian and Dahuabai, on the contrary, 314 bp indel segregates only in Duroc and Landrace. C1801T and T1806C sites seem to be completely linked and segregate in Erhualian, Dahuabai and Landrace. In a word, GDF9 may be not associated with pig litter size in extensive populations as per the studies of allele distributions of the four polymorphisms and pilot association in four breeds.

Differences in brain-derived neurotrophic factor gene polymorphisms between acute ischemic stroke patients and healthy controls in the Han population of southwest China

Single-nucleotide polymorphisms in the brain-derived neurotrophic factor gene may affect the secretion and function of brain-derived neurotrophic factor, thereby affecting the occurrence, severity and prognosis of ischemic stroke. This case-control study included 778 patients (475 males and 303 females, mean age of 64.0 ± 12.6 years) in the acute phase of ischemic stroke and 865 control subjects (438 males and 427 females, mean age of 51.7 ± 14.7 years) from the Department of Neurology, Wes: China Hospital, Sichuan University, China between September 2011 and December 2014. The patients' severities of neurological defici:s in the acute phase were assessed using the National Institutes of Health Stroke Scale immediately after admission to hospital. The ischemic stroke patients were divided into different subtypes according to the Trial of Org 10172 in Acute Stroke Treatment classification. Early prognosis was evaluated using the Modified Rankin Scale when the patients were discharged. Genomic DNA was extracted from peripheral blood of participants. Genotyping of rs7124442 and rs6265 was performed using Kompetitive Allele Specific polymerase chain reaction genotyping technology. Our results demonstrated that patients who carried the C allele of the rs7124442 locus had a lower risk of poor prognosis than the T allele carriers (odds ratio [OR]= 0.67;95% confidence interval [CI]: 0.45-1.00;P = 0.048). The patients with the CC or TC genotype also exhibited lower risk than TT carriers (OR = 0.65;95% CI: 0.42-1.00;P = 0.049). The AA genotype at the rs6265 locus was associated with the occurrence of ischemic stroke in patients with large-artery atherosclerosis (OR = 0.5& 95% CI: 0.37-0.90;P = 0.015). We found that the C allele (CC and TC genotypes) at the rs7124442 locus may be protective for the prognosis of ischemic stroke. The AA genotype at the rs6265 locus is likely a protective factor against the occurrence of ischemic stroke in patients with large-artery atherosclerosis. The study protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval ID number 2008,4]) on July 25, 2008.