XRCC4 c.1394G>T Single Nucleotide Polymorphisms and Breast Cancer Risk among Filipinos

Background: The identification of cancer-associated single nucleotide polymorphisms (SNP) and mutationgenes is a promising approach in recognizing individuals who are at risk of developing cancer. Hence, this studywas conducted to determine the association between XRCC4 c.1394G>T SNP and breast cancer development amongFilipinos. Methods: Genotyping for XRCC4 c.1394G>T SNP was performed on breast cancer patients (n=103) andtheir age- and sex- matched clinically healthy controls (n=103) by polymerase chain reaction – restriction fragmentlength polymorphism. Results: Significant difference in genotype (p=0.007) and allele (p=0.003) frequencies in XRCC4c.1394G>T was observed between the breast cancer cases and controls. Carriers of the XRCC4 c.1394 G>T genotypewere observed to have significantly higher risk of developing breast cancer compared to individuals with T/T genotype(OR=2.67, 95% CI: 1.36 – 5.25). XRCC4 c.1394G>T combined with passive smoking may also significantly increaserisk of breast cancer (OR=14.73; 95% CI= 9.88-18.86). Conclusion: XRCC4 c. 1394G>T may be associated withbreast cancer development among Filipinos.     

Genetic Variation in MicroRNAs and Risk of Oral Squamous Cell Carcinoma in South Indian Population

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules, implicated in several activities like initiation, progression and prognosis of various cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes can lead to alteration in mRNA expression, resulting in diverse functional consequences. The aim of our study was to investigate the association of miR-149C>T and miR-196a2C>T SNPs with susceptibility to development of oral squamous cell carcinoma (OSCC) in South Indian subjects. Materials and Methods: 100 OSCC patients and 102 healthy controls from the general population were recruited for the study. Genetic analysis was performed by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) as per a standard protocol. Results: The genotype frequencies in miR-196a2 polymorphism, of TT, CT and CC in the OSCC patients were 69%,10% and 22% respectively while for control group it was 80%, 15% and 5% respectively. The CC genotype of miR196a2 polymorphism was significantly associated with oral squamous cell carcinoma. The genotype frequencies in miR-149 polymorphisms of CC, CT and TT in the oral squamous cell carcinoma (OSCC) patients were 72%, 22% and 6% respectively and for control group 88%, 12% and 0% respectively. CT and TT genotypes of miR149 polymorphism were found to be significantly associated with OSCC (p = 0.05 and 0.07). Conclusions: Our study suggests that miR-196a2C>T and miR-149C>T polymorphisms may play crucial roles in the development of OSCC in South Indian subjects.     

HSP70-hom基因多态性与高原反应易感性的关系

目的 探讨热应激或热休克蛋白70-hom(HSP70-hom)基因型与高原反应易感性间的关系,为发现和保护易感人群提供依据。方法随机选取武警战士229人,其中56人有高原反应者为病例组,173人无高原反应者为对照组。应用聚合酶链反应～限制性片段长度多态性(PCR-RFLP)分析方法,研究两组观察对象中HSP70-hom的基因型分布情况。结果病例组HSP70-hom A／A基因型的频率明显高于对照组,差异有显著性(P＜0．05)。结论 HSP70-hom A／A基因型的机体可能存在应激能力较弱的问题,这有助于在特定职业人群中发现和保护这些个体,为保障健康,提高工作效率提供科学依据。     

Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker＇s Pneumoconiosis

Objectives Tumor necrosis factor-α （TNF-α） may play an important role in host＇s immune response to mycobacterium tuberculosis （M. tuberculosis） infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis （TB） among patients with coal worker＇s pneumoconiosis （CWP）. Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism （PCR-RFLP）. Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher＇s exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls （2,2=5.44, P=-0.07）. But difference in frequency of the TNF-α-308 A allele was identified between them （2,2-5.14, P=0.02）. No significant difference in frequencies of the TNF-α-238 genotype and allele （P=0.23 and P=0.09, respectively） was found between cases and controls either, with combined （GG and AA） OR of 3.96 （95% confidence interval of 1.30-12.09） at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 （95% CI of 1.06-3.71） for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index （OR=4.92）, as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.     

Maternal gene polymorphisms involved in folate metabolism as risk factors for Down syndrome offspring in Southern Brazil

This study aimed to investigate the role of maternal polymorphisms, as well as their risk genotypes combinations of MTR A2756G, MTRR A66G, CBS 844ins68, and RFC A80G, involved in folate/homocysteine metabolism, as possible risk factors for Down syndrome (DS) in Southern Brazil. A case-control study was conducted with 239~mothers of DS children and 197~control mothers. The investigation of polymorphisms was performed by PCR and PCR-RFLP. The distribution of genotypic variants was similar in both groups when they were analyzed separately. An investigation of combined risk genotypes showed that the risk of having a DS child for one, two or three risk genotypes was 6.23, 6.96 and 5.84 (95%CI 1.48-26.26; 1.69-28.66; 1.37-24.86), respectively. The combined MTRR 66G and MTHFR 677T alleles were significantly more common among mothers of children with DS than among control mothers (OR 1.55; IC 95% 1.03-2.35). The results show that individual polymorphisms studied in this work are not associated with DS; however, the effects of the combined risk genotypes among MTR, MTRR, CBS and RFC genes are considered maternal risk factors for DS offspring in our population.     

PTEN基因Ⅳ S4多态性与乳腺癌易感相关性分析

目的:初步探索PTEN基因ⅣS4位点多态性与群乳腺癌易感性之间的相关性。方法:采用基于人群的病例-对照研究,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行基因分型,检测210例乳腺癌患者和210例健康女性的PTEN基因ⅣS4位点多态性。用非条件Logistic回归方法计算比值比OR值及95%CI。结果:与PTEN基因ⅣS4-/-基因型相比,ⅣS4+/+基因型显著降低乳腺癌的发病风险(校正的OR=0.610,95%CI:0.380～0.980,P=0.041)。结论:PTEN基因ⅣS4位点ⅣS4+/+基因型是乳腺癌发病的保护性因素。     

维吾尔族人群代谢性疾病与ApoEε2等位基因

目的探讨维吾尔族代谢性疾病与载脂蛋白Eε2等位基因(ApoEε2)的关系。方法收集2006年1月-2006年12月在新疆医科大学附属中医医院和宝科达医院健康体检的386名维吾尔族人,采集血液标本,检测血液生化指标以及ApoE基因型。结果新疆维吾尔族ApoEε2等位基因的携带率为31.9%(123/386);与非携带组比较,除了高密度脂蛋白-胆固醇升高外,ApoEε2等位基因携带组的其余指标均有下降趋势,其中收缩压、舒张压及低密度脂蛋白差异有统计学意义(P0.05);与非携带组比较,携带者代谢性疾病检出率降低,尤其是对高胆固醇血症和高血压影响较大,其中高血压检出率差异,P=0.058。结论ApoEε2等位基因携带者血脂水平及代谢性疾病的检出率降低,是代谢性疾病的保护因素。     

Association of Genetic Variants of the Vitamin D Receptor (VDR) Gene (Fok-I,Taq-I & Bsm-I) with Susceptibility of Benign Prostatic Hyperplasia in a North Indian Population

Several genetic studies worldwide have recommended VDR as candidate gene for determining risk of benign prostate hyperplasia (BPH). We investigated the association between VDR gene polymorphisms and the risk of BPH in an Indian male population. Three polymorphic sites of VDR gene, viz., Fok-I, Taq-I and Bsm-I were genotyped in 160 BPH patients and 160 controls. Logistic regression models were used to determine the genetic effects using SPSS statistical software. A statistically significant association between VDR genotype (Taq-I and Bsm-I) and BPH (p=0.02 & 0.03) was obtained. In exploratory analyses, we also examined the association with responder and non-responder subgroups of patients for association of VDR (Taq-I) genotype with drug responsiveness. Our results established that Taq-I and Bsm-I genetic variants of VDR gene influence susceptibility BPH in Indian population. VDR genotypes specifically, Taq-I polymorphic variant is significantly associated with the improvement of BPH patients with standard drug therapy.     

Lack of Influence of MGMT Codon Leu84Phe and Codon Ileu143Val Polymorphisms on Esophageal Cancer Risk in the Kashmir Valley

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA bycarcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrationsof these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their riskof esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codonLeu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked topredisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reactionrestrictionfragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs ofthe MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly,the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, nosignificant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients wasobserved. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility ofthe Kashmiri population to esophageal cancer.