Association between Polymorphism of the Interleukin-13 Gene and Susceptibility to Hepatocellular Carcinoma in the Chinese Population

ObjectiveInterleukin-13 (IL-13) is a potent pleiotropic cytokine that is produced by activated CD4 T cells. This study was undertaken to determine the relationship between two IL-13 gene single nucleotide polymorphisms (SNP rs1800925 and SNP rs20541) and the incidence of hepatitis B virus-related (HBV) hepatocellular carcinoma (HCC).MethodThree hundred and ninety-eight HBV-positive individuals (192 HCC and 206 patients with chronic hepatitis) and one hundred and ninety-two healthy participants from the First Affiliated Hospital of Guangxi Medical University were enrolled in this study.ResultsThe results showed no significant differences between the genotype and allele frequencies of the IL-13 gene rs1800925 and rs20541 polymorphisms and chronic hepatitis B risk after adjusting for age, sex, tobacco use, and alcohol intake using binary logistic regression analyses. Regarding the rs20541 SNP, the GA genotype was significantly related to a decreased risk of HCC after adjusting for age, sex, tobacco use, and alcohol intake using binary logistic regression analyses (The odds ratio (OR) = 0.54, 95% confidence intervals (CI) 0.34–0.87). The adjusted OR for the GA and AA genotypes combined was 0.68 (95% CI 0.39–0.90).ConclusionThis study indicates that the functional IL-13 rs20541 polymorphism may contribute to the risk of HCC and that the rs20541 polymorphism is a protective factor for HCC.     

A Single Nucleotide Polymorphism of Chicken Acetyl-CoA Carboxylase A Gene Associated with Fatness Traits

Acetyl-CoA carboxylase α (ACCα) is a major rate-limiting enzyme in the biogenesis of long-chain fatty acids. It can catalyze the carboxylation of acetyl-CoA to form malonyl-CoA that plays a key role in the regulation of fatty acid metabolism. The objective of the present study was to investigate the associations of ACCα gene polymorphisms with chicken growth and body composition traits. The Northeast Agricultural University broiler lines divergently selected for abdominal fat content and the Northeast Agricultural University F₂ Resource Population were used in the current study. Body weight and body composition traits were measured in the aforementioned two populations. A synonymous mutation was detected in the exon 19 region of ACCα gene, then polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was developed to genotype all the individuals derived from the aforementioned populations. Association analysis revealed that the polymorphism was associated with abdominal fat weight and percentage of abdominal fat in the two populations. The results suggested that ACCα gene could be a candidate locus or linked to a major gene that affects abdominal fat content in the chicken.     

A Single Nucleotide Polymorphism within DUSP9 Is Associated with Susceptibility to Type 2 Diabetes in a Japanese Population

Aims

The DUSP9 locus on chromosome X was identified as a susceptibility locus for type 2 diabetes in a meta-analysis of European genome-wide association studies (GWAS), and GWAS in South Asian populations identified 6 additional single nucleotide polymorphism (SNP) loci for type 2 diabetes. However, the association of these loci with type 2 diabetes have not been examined in the Japanese. We performed a replication study to investigate the association of these 7 susceptibility loci with type 2 diabetes in the Japanese population.

Methods

We genotyped 11,319 Japanese participants (8,318 with type 2 diabetes and 3,001 controls) for each of the 7 SNPs–rs5945326 near DUSP9, rs3923113 near GRB14, rs16861329 in ST6GAL1, rs1802295 in VPS26A, rs7178572 in HMG20A, rs2028299 near AP3S2, and rs4812829 in HNF4A–and examined the association of each of these 7 SNPs with type 2 diabetes by using logistic regression analysis.

Results

All SNPs had the same direction of effect (odds ratio [OR]>1.0) as in the original reports. One SNP, rs5945326 near DUSP9, was significantly associated with type 2 diabetes at a genome-wide significance level (p = 2.21×10⁻⁸; OR 1.39, 95% confidence interval [CI]: 1.24−1.56). The 6 SNPs derived from South Asian GWAS were not significantly associated with type 2 diabetes in the Japanese population by themselves (p≥0.007). However, a genetic risk score constructed from 6 South Asian GWAS derived SNPs was significantly associated with Japanese type 2 diabetes (p = 8.69×10⁻⁴, OR  = 1.06. 95% CI; 1.03−1.10).

Conclusions/interpretation

These results indicate that the DUSP9 locus is a common susceptibility locus for type 2 diabetes across different ethnicities, and 6 loci identified in South Asian GWAS also have significant effect on susceptibility to Japanese type 2 diabetes.     

A Non-Synonymous Single Nucleotide Polymorphism in an OPRM1 Splice Variant Is Associated with Fentanyl-Induced Emesis in Women Undergoing Minor Gynaecological Surgery

Background

Fentanyl-induced emesis (FIE) is a distressing adverse effect in the postoperative setting. The genetic basis of FIE remains largely unknown, therefore, we examined whether it was associated with specific genetic variants of OPRM1, the gene encoding the main receptor target of fentanyl.

Methods

In this prospective case-control study, 193 women undergoing gynaecological surgery under a standardized anaesthetic with a low emetogenic risk were enrolled. Inclusion and exclusion criteria were designed to select extreme phenotypes as well as to ensure that most major confounders for FIE were either excluded or present in all patients. To control for unforeseen intra- and postoperative confounders for FIE, only 161 patients were further analysed, out of which 10 were categorized as having FIE, defined by the presence of at least one of three symptoms: nausea, vomiting or retching that was likely to be fentanyl-related. To identify SNPs relevant to FIE in our population, DNA from 40 controls and 10 cases was sequenced at the following OPRM1 regions: 3 kbp of the promoter, main and alternative exons as well as 2 kbp of the 3′ downstream region. The genotype of the significant SNP was further determined in the remaining 111 controls.

Results

The incidence of FIE was 6.2%. Initial sequencing of 10 cases and 40 controls identified 25 SNPs. Only rs540825, a non-synonymous SNP in the splice variant, MOR1X, showed a significant association with FIE post-Bonferroni correction. This SNP was further examined in the remaining 111 controls which confirmed its significant association with FIE (p = 0.019 post-Bonferroni, OR: 5.6, 95% CI: 1.42–21.91).

Conclusions

This is the first report of an association between the occurrence of FIE in Chinese women undergoing gynaecological surgery and an OPRM1 splice variant SNP, rs540825.     

A Functional Insertion/Deletion Polymorphism in the Proximal Promoter of CD3G Is Associated with Susceptibility for Hepatocellular Carcinoma in Chinese Population

Hepatocellular carcinoma (HCC) represents the most common primary malignancy of the liver with a worldwide increasing incidence. Although the risk factors for HCC are well characterized, the molecular mechanisms responsible for malignant transformation of hepatocytes are not well understood. In this study, a case-control study including 291 HCC patients and 294 healthy controls was conducted to investigate the association between HCC susceptibility and with a 4-bp insertion/deletion polymorphism (rs66465034) in the proximal promoter of CD3G. Logistic regression analysis showed that the heterozygote and the homozygote 4-bp ins/ins confer a significantly increased risk of HCC after controlling for other covariates (adjusted odds ratio [OR]=1.51, 95% confidence interval [C.I.] 1.01-2.27, p=0.040; OR=1.71, 95% C.I. 1.07-2.89, p=0.025, respectively). Carriage of the 4-bp insertion allele was associated with a greatly increased risk of developing the disease (OR=1.30, 95% C.I. 1.02-1.64, p=0.027). Moreover, hepatitis B virus (HBV) stratification analysis showed that the differences between cases and controls were more obvious in HBV-positive than in the HBV-negative population, suggesting a possible role of this polymorphism in the immune regulation during HBV infection. Further, luciferase-based transient transfection assays revealed that rs66465034 can affect promoter activity of CD3G, indicating its possible functional significance. Our data suggested that common genetic polymorphisms in CD3G may influence HCC risk in Chinese population. Considering the relative small sample size, replication in other populations with larger sample size and further functional analysis are required for fully understanding the roles of CD3G polymorphisms in predisposition for HCC.     

A Single Nucleotide Polymorphism in Catalase Is Strongly Associated with Ovarian Cancer Survival

Ovarian cancer is the deadliest of all gynecologic cancers. Recent evidence demonstrates an association between enzymatic activity altering single nucleotide polymorphisms (SNP) with human cancer susceptibility. We sought to evaluate the association of SNPs in key oxidant and antioxidant enzymes with increased risk and survival in epithelial ovarian cancer. Individuals (n = 143) recruited were divided into controls, (n = 94): healthy volunteers, (n = 18), high-risk BRCA1/2 negative (n = 53), high-risk BRCA1/2 positive (n = 23) and ovarian cancer cases (n = 49). DNA was subjected to TaqMan SNP genotype analysis for selected oxidant and antioxidant enzymes. Of the seven selected SNP studied, no association with ovarian cancer risk (Pearson Chi-square) was found. However, a catalase SNP was identified as a predictor of ovarian cancer survival by the Cox regression model. The presence of this SNP was associated with a higher likelihood of death (hazard ratio (HR) of 3.68 (95% confidence interval (CI): 1.149–11.836)) for ovarian cancer patients. Kaplan-Meier survival analysis demonstrated a significant median overall survival difference (108 versus 60 months, p<0.05) for those without the catalase SNP as compared to those with the SNP. Additionally, age at diagnosis greater than the median was found to be a significant predictor of death (HR of 2.78 (95% CI: 1.022–7.578)). This study indicates a strong association with the catalase SNP and survival of ovarian cancer patients, and thus may serve as a prognosticator.     

Single Nucleotide Polymorphism in ATM Gene,Cooking Oil Fumes and Lung Adenocarcinoma Susceptibility in Chinese Female Non-Smokers: A Case-Control Study

Background

The ataxia-telangiectasia mutated (ATM) gene plays an important role in the DNA double-strand breaks repair pathway. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence the risk of lung cancer. This study aimed to investigate the association between the ATM -111G>A (rs189037) polymorphism, environmental risk factors and the risk of lung adenocarcinoma in Chinese female non-smokers.

Methods

A hospital-based case-control study of 487 lung cancer patients and 516 matched cancer-free controls was conducted. Information concerning demographic and environmental risk factors was obtained for each case and control by a trained interviewer. After informed consent was obtained, 10 ml venous blood was collected from each subject for biomarker testing. Single nucleotide polymorphism was determined by using TaqMan method.

Results

This study showed that the individuals with ATM rs189037 AA genotype were at an increased risk for lung adenocarcinoma compared with those carrying the GA or GG genotype (adjusted odds ratios (OR) 1.44, 95% confidence interval (CI) 1.02–2.02, P = 0.039). The stratified analysis suggested that increased risk associated with ATM rs189037 AA genotype in individuals who never or seldom were exposed to cooking oil fumes (adjusted OR 1.89, 95%CI 1.03–3.49, P = 0.040).

Conclusions

ATM rs189037 might be associated with the risk of lung adenocarcinoma in Chinese non-smoking females. Furthermore, ATM rs189037 AA genotype might be a risk factor of lung adenocarcinoma among female non-smokers without cooking oil fume exposure.     

Computational Screening and Molecular Dynamic Simulation of Breast Cancer Associated Deleterious Non-Synonymous Single Nucleotide Polymorphisms in TP53 Gene

Breast cancer is one of the most common cancers among the women around the world. Several genes are known to be responsible for conferring the susceptibility to breast cancer. Among them, TP53 is one of the major genetic risk factor which is known to be mutated in many of the breast tumor types. TP53 mutations in breast cancer are known to be related to a poor prognosis and chemo resistance. This renders them as a promising molecular target for the treatment of breast cancer. In this study, we present a computational based screening and molecular dynamic simulation of breast cancer associated deleterious non-synonymous single nucleotide polymorphisms in TP53. We have predicted three deleterious coding non-synonymous single nucleotide polymorphisms rs11540654 (R110P), rs17849781 (P278A) and rs28934874 (P151T) in TP53 with a phenotype in breast tumors using computational tools SIFT, Polyphen-2 and MutDB. We have performed molecular dynamics simulations to study the structural and dynamic effects of these TP53 mutations in comparison to the wild-type protein. Results from our simulations revealed a detailed consequence of the mutations on the p53 DNA-binding core domain that may provide insight for therapeutic approaches in breast cancer.     

Prediction of the Damage-Associated Non-Synonymous Single Nucleotide Polymorphisms in the Human MC1R Gene

The melanocortin 1 receptor (MC1R) is involved in the control of melanogenesis. Polymorphisms in this gene have been associated with variation in skin and hair color and with elevated risk for the development of melanoma. Here we used 11 computational tools based on different approaches to predict the damage-associated non-synonymous single nucleotide polymorphisms (nsSNPs) in the coding region of the human MC1R gene. Among the 92 nsSNPs arranged according to the predictions 62% were classified as damaging in more than five tools. The classification was significantly correlated with the scores of two consensus programs. Alleles associated with the red hair color (RHC) phenotype and with the risk of melanoma were examined. The R variants D84E, R142H, R151C, I155T, R160W and D294H were classified as damaging by the majority of the tools while the r variants V60L, V92M and R163Q have been predicted as neutral in most of the programs The combination of the prediction tools results in 14 nsSNPs indicated as the most damaging mutations in MC1R (L48P, R67W, H70Y, P72L, S83P, R151H, S172I, L206P, T242I, G255R, P256S, C273Y, C289R and R306H); C273Y showed to be highly damaging in SIFT, Polyphen-2, MutPred, PANTHER and PROVEAN scores. The computational analysis proved capable of identifying the potentially damaging nsSNPs in MC1R, which are candidates for further laboratory studies of the functional and pharmacological significance of the alterations in the receptor and the phenotypic outcomes.     

Association of the FCN2 Gene Single Nucleotide Polymorphisms with Susceptibility to Pulmonary Tuberculosis

Ficolin-2 (FCN2) is an innate immune pattern recognition molecule that can activate the complement pathway, opsonophagocytosis, and elimination of the pathogens. The present study aimed to investigate the association of the FCN2 gene single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (TB). A total of seven SNPs in exon 8 (+6359 C>T and +6424 G>T) and in the promoter region (-986 G>A, -602 G>A, -557 A>G, -64 A>C and -4 A>G) of the FCN2 gene were genotyped using the PCR amplification and DNA sequencing methods in the healthy controls group (n = 254) and the pulmonary TB group (n = 282). The correlation between SNPs and pulmonary TB was analyzed using the logistic regression method. The results showed that there were no significant differences in the distribution of allelic frequencies of seven SNPs between the pulmonary TB group and the healthy controls group. However, the frequency of the variant homozygous genotype (P = 0.037, -557 A>G; P = 0.038, -64 A>C; P = 0.024, +6424 G>T) in the TB group was significantly lower than the control group. After adjustment for age and gender, these variant homozygous genotypes were found to be recessive models in association with pulmonary TB. In addition, -64 A>C (P = 0.047) and +6424 G>T (P = 0.03) were found to be codominant models in association with pulmonary TB. There was strong linkage disequilibrium (r² > 0.80, P < 0.0001) between 7 SNPs except the -602 G>A site. Therefore, -557 A>G, -64 A>C and +6424 G>T SNPs of the FCN2 gene were correlated with pulmonary TB, and may be protective factors for TB. This study provides a novel idea for the prevention and control of TB transmission from a genetics perspective.     

rs3746444 Polymorphism and Susceptibility to Hepatocellular Carcinoma: Evidence from Published Studies

The present study was undertaken to quantitatively evaluate the association between rs3746444 polymorphism and HCC risk. In this analysis with 667 cancer cases and 1,006 control subjects, we summarized 4 eligible case–control studies by searching databases of PubMed, EMBASE, and CNKI. The strength of the association was assessed by calculating odds ratios (ORs) with 95 % confidence intervals (CIs) with the fixed-effects model. We found that neither the allele frequency nor genotype distribution of this polymorphism was associated with risk of HCC in any genetic model. Similarly, no associations were suggested either in subgroup analyses by ethnicity or by source of control. Our research suggested that rs3746444 polymorphism may not be a risk factor for HCC. However, well-designed studies with a larger sample size are needed to confirm these findings.     

中国美利奴羊H-FABP基因多态性及其与部分肉质性状相关性的研究

利用聚合酶链式反应-单链构象多态（PCR-SSCP）技术检测中国美利奴羊(Chinese Merino)心脏型脂肪酸结合蛋白基因（H-FABP）外显子2的单核苷酸多态性（SNPs）和遗传多态性,分析其与肌内脂肪（IMF）含量、肌纤维直径和肌纤维密度的相互关系,为该品种绵羊的分子标记辅助选择提供理论依据。结果显示,H-FABP基因外显子2有AA、AB和BB 3种基因型,AA型和BB型在778位均发生了C缺失,939位均发生了A→G转换,BB型还在789位发生了T→C转换,该突变导致所编码氨基酸发生了缬氨酸→丙氨酸的替换;BB型为IMF的优势基因型,与AB型相比差异显著(P<0.05),与AA型相比差异极显著（P<0.01);BB型对肌纤维直径存在负相关。结果提示,中国美利奴羊H-FABP基因外显子2具有多态性,该基因可能是中国美利奴羊肉质性状的主效基因,或者与控制这些性状的主效基因相连锁。     

Non-Synonymous SNP in the ApoR Gene Associated with Pork Meat Quality

Two novel non-synonymous SNPs in the 2^nd and 3^rd exons of the porcine ApoR gene are reported. One was identified as a novel SNP significantly associated with multiple traits of pork meat quality. The data can provide a useful resource for developing a marker in the genetic improvement of pigs.     

猪Mu阿片受体基因单核苷酸多态性分析

Mu阿片受体（简称MOR）属于G蛋白藕联受体,分布在痛觉传导区,以及与情绪和行为有关的区域,影响动物的神经反应和行为表现。该研究以长白猪、大白猪和杜洛克猪为试验材料, 用8对引物对Mu阿片受体基因的5′ UTR区域、整个编码区和3′ UTR区域用PCR-SSCP方法进行了扫描,发现5处突变基因座（GenBank登录号：AF521309）。统计结果发现基因型频率分布与品种有关,大白猪突变基因型频率显著高于长白和杜洛克,本研究推测分布上的差异可能是由于长期的选择压力造成的。 Abstract:Mu opioid receptor (MOR) is a member of G protein-coupled receptor family,distributed in the pain transduction region in the brain and related to emotion and behaviour.This study was designed to investigate the Single Nucleotide Polymorphism (SNP) of Mu opioid receptor gene in various breeds,including duroc,landrace and Yorkshire.5′ UTR ( untranslate region),coding region and 3′ UTR of Mu opioid receptor gene were amplified by eight pairs of primers,and the Single Nucleotide Polymorphism (SNP) were detected by SSCP.Five polymorphisms were found (Genebank Accession number:AF521309).The results of χ2 test showed that the frequencies of genotypes in different breeds were significantly different (P＜0.01).The frequencies of mutation genotypes in Yorkshire were significantly higher than Duroc and Landrace.According to the above results,we can speculate the difference of the frequencies of genotypes may be the results of long term choice pressure.     

E-钙粘蛋白基因启动子区域单核苷酸基因多态性(-347G→GA)和大肠癌遗传易感性的联系

目的:探讨E-钙粘蛋白基因(CDH1)启动子区域-347G→GA单核苷酸基因多态性(single nucleotide polymorphism,SNP)和中国地区散发大肠癌(colorectal cancer,CRC)人群遗传易感性的联系.方法:以中国地区大肠癌病人群为研究基础,同时建立无肿瘤家族史以及其它遗传性疾病史的正常对照组,进行病例对照研究,采用聚合酶链反应一限制性片段长度多态性技术(poly-merase chain reaction-restriction fragment length polymorphism,PCR-RFLP)行目的基因的多态性测定.结果:正常对照组和大肠癌组的目的基因型分布频率并无统计学差异(x2检验,P=0.246),而近端大肠癌患者中GA基因型(GA/GA杂合子和GA/GA纯合子)比例明显高于对照组(OR=1.773,95%CI=1.174-2.679,P=0.007),同时低分化大肠腺癌GA基因型比例也明显高于对照组(OR=2.623,95%CI=1.326-5.191,P=0.007).结论:CDHl启动子区域-347G→GA单核苷酸基因多态性中GA基因型可能增加近端大肠癌以及低分化腺癌的发病风险.     

Caveolin-1 Single Nucleotide Polymorphism in Antineutrophil Cytoplasmic Antibody Associated Vasculitis

Objective

Immunosuppression is cornerstone treatment of antineutrophil cytoplasmic antibody associated vasculitis (AAV) but is later complicated by infection, cancer, cardiovascular and chronic kidney disease. Caveolin-1 is an essential structural protein for small cell membrane invaginations known as caveolae. Its functional role has been associated with these complications. For the first time, caveolin-1 (CAV1) gene variation is studied in AAV.

Methods

CAV1 single nucleotide polymorphism rs4730751 was analysed in genomic DNA from 187 white patients with AAV from Birmingham, United Kingdom. The primary outcome measure was the composite endpoint of time to all-cause mortality or renal replacement therapy. Secondary endpoints included time to all-cause mortality, death from sepsis or vascular disease, cancer and renal replacement therapy. Validation of results was sought from 589 white AAV patients, from two European cohorts.

Results

The primary outcome occurred in 41.7% of Birmingham patients. In a multivariate model, non-CC genotype variation at the studied single nucleotide polymorphism was associated with increased risk from: the primary outcome measure [HR 1.86; 95% CI: 1.14-3.04; p=0.013], all-cause mortality [HR:1.83; 95% CI: 1.02-3.27; p=0.042], death from infection [HR:3.71; 95% CI: 1.28-10.77; p=0.016], death from vascular disease [HR:3.13; 95% CI: 1.07-9.10; p=0.037], and cancer [HR:5.55; 95% CI: 1.59-19.31; p=0.007]. In the validation cohort, the primary outcome rate was far lower (10.4%); no association between genotype and the studied endpoints was evident.

Conclusions

The presence of a CC genotype in Birmingham is associated with protection from adverse outcomes of immunosuppression treated AAV. Lack of replication in the European cohort may have resulted from low clinical event rates. These findings are worthy of further study in larger cohorts.     

Variants Identified by Hepatocellular Carcinoma and Chronic Hepatitis B Virus Infection Susceptibility GWAS Associated with Survival in HBV-Related Hepatocellular Carcinoma

Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of hepatocellular carcinoma (HCC) or chronic hepatitis B infection (CHB). However, the relationship between these genetic variants and survival of patients with hepatitis B virus (HBV)-related HCC is still unknown. In this study, 22 single nucleotide polymorphisms (SNPs) were genotyped among 330 HBV-related HCC patients using the MassARRAY system from Sequenom. Cox proportional hazards regression was used to examine the effects of genotype on survival time under an additive model with age, sex, smoking status and clinical stage as covariates. We identified four SNPs on 6p21 (rs1419881 T>C, rs7453920 G>A,rs3997872 G>A and rs7768538 T>C), and two SNPs on 8p12 (rs2275959 C>T and rs7821974 C>T) significantly associated with survival time of HBV-related HCC patients. Our results suggest that HCC or CHB susceptibility loci might also affect the prognosis of patients with HBV-related HCC.     

中国人MTHFR基因多态性与神经管畸形遗传易感性

目的：应用分子生物学方法进行遗传流行病学研究, 探讨MTHFR基因多态性在神经管畸形的遗传易感性中的作用。方法：应用PCR?RFLP方法检测MTHFR热敏感性基因型;对18个NTD核心家庭进行以父母为对照的病例对照研究,计算TDT和HHRR;另外对31例NTD胎儿和62例正常成年人进行的成组病例对照研究,计算MTHFR纯合突变对NTD的比值比。结果：核心家庭分析结果：比值比OR=3.2,95％CI=1.120～11.169;TDT（χ2）=5.762,P<0.05,HHRR（成组χ2）=6.727,P<0.05;胎儿MTHFR纯合突变对NTD的相对危险度OR=3?21,P<0?05。结论：研究结果说明,突变等位基因在神经管畸形核心家庭中存在突变基因(T)的遗传失衡现象,胎儿MTHFR基因第677位核苷酸的多态性是中国人NTD遗传易感性因素之一。 Abstract：The objective of the study is to clarify the effect of MTHFR thermolabile polymorphism on genetic susceptibility of NTD in Chinese population.MTHFR genotypes were detected using PCR-RFLP analysis; 18 NTD nuclear families were analysed as case-parental control study,from which Transmitted Disequillibrium Test(TDT) and Haplotype-based Haplotype Relative Risk (HHRR) were calculated; 31 NTD fetuses and 62 adult controls were analysed for calculation of OR of homozygotic MTHFR.The results are as follow:Nuclear family analysis: OR=3.2( 95％CI=1.120～11.169);TDT（paired χ2）=5.762,P<0.05,HHRR（χ2）=6.727,P<0.05;homozygotic MTHFR of fetus vs adult control: OR=3.21,P<0.05. The 677th allele of MTHFR is abnormally transmitted in NTD nuclear families.Homozygotic MTHFR of the fetus may be a genetic factor of NTD in China.     

Association of Single Nucleotide Polymorphisms in VDR and DBP Genes with HBV-Related Hepatocellular Carcinoma Risk in a Chinese Population

Background

Polymorphisms of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (DBP) have been widely investigated because of the complex role played by vitamin D in cancer tumorogenesis. In this study, we investigated the association between VDR and DBP gene polymorphisms and HBV-related HCC risk in a Chinese population.

Methods

Study subjects were divided into three groups: 184 HBV patients with HCC, 296 HBV patients without HCC, and 180 healthy controls. The VDR rs2228570, and rs3782905 and the DBP rs7041 polymorphisms were genotyped using PCR-RFLP and the VDR rs11568820 polymorphism was genotyped by PCR-SSP, respectively. DNA sequencing was performed to validate the genotype results.

Results

We found that there were significant differences in the genotype and allele frequencies of the VDR rs2228570 and DBP rs7041 polymorphisms between HBV patients with HCC and healthy controls. The rs2228570 T allele was associated with a significant increased HBV-related HCC risk as compared with the C allele. The rs2228570 TT and TT/TC genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type CC homozygote. Similarly, the rs7041 G allele was associated with a significant increased HBV-related HCC risk as compared with the T allele. The rs7041 GG and GG/TG genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type TT homozygote. However, we did not observe any significant effect of VDR rs11568820, and rs3782905 polymorphisms on HBV-related HCC risk in this population. In haplotype analysis, we also did not find any significant differences in haplotype frequencies of the VDR gene between HBV patients with HCC and the healthy controls.

Conclusions

We conclude that the VDR rs2228570 and DBP rs7041 polymorphisms may contribute to increased susceptibility to HBV-related HCC in the Chinese population. Due to the marginal significance, further large and well-designed studies in diverse ethnic populations are needed to confirm our results.