DNA repair polymorphisms might contribute differentially on familial and sporadic breast cancer susceptibility: a study on a Portuguese population

The purpose of this study was to evaluate the role of polymorphisms in DNA repair genes as genetic indicators of susceptibility to familial and sporadic breast cancer. We analysed DNA samples from 285 breast cancer patients and 442 control subjects, for XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met polymorphisms using PCR-RFLP. We observed that women carriers of XRCC1 399Gln genotypes and without family history of breast cancer have a protective effect concerning this disease (OR = 0.54 95% CI 0.35–0.84; p = 0.006). Furthermore, we found that carriers of XRCC3 241Met genotypes without FH have an increased susceptibility of breast cancer (OR = 2.21 95% CI 1.42–3.44; p < 0.001). Additionally, we verified an increased risk of breast cancer in women with FH and carrying RAD51 135C genotypes (OR = 2.17 95% CI 1.19–3.98; p = 0.012). Our results suggest XRCC1 Arg399Gln and XRCC3 Thr241Met DNA repair polymorphisms as important biomarkers to sporadic breast cancer susceptibility, as well as, RAD51 G135C polymorphism as a real risk modifier in familial breast cancer cases.     

Impact of DNA repair,folate and glutathione gene polymorphisms on risk of non small cell lung cancer

Lung cancer, particularly non-small cell lung cancer (NSCLC) subtype, is the leading cause of cancer-related death related worldwide. Numerous gene polymorphisms in DNA repair, folate and glutathione pathways have been associated with susceptibility of NSCLC. We conducted this study to evaluate the effects of ERCC1, ERCC2, ERCC5, XRCC1, XRCC3, MTHFR, MTR, MTHFD1, SLC19A1 and GSTP1 gene polymorphisms on risk of NSCLC.No association between these gene polymorphisms and susceptibility of NSCLC were found in our patients, suggesting that genetic variations in genes involved in DNA repair, folate and glutathione metabolism pathways may not influence the risk of NSCLC.     

2型糖尿病肥胖患者CXCL5基因多态性的研究

探讨CXCL5启动子-156G/C基因多态性与肥胖2型糖尿病的关系.结果显示该基因多态性在2型糖尿病组与对照组的分布差异无统计学意义(P＞0.05),而肥胖者C等位基因频率高于非肥胖者,差异有统计学意义(P＜0.05).提示趋化因子CXCL5-156G/C基因变异不是糖尿病发病的危险因素,有可能是引起肥胖的重要遗传因素.     

JAG1 and COL1A1 polymorphisms and haplotypes in relation to bone mineral density variations in postmenopausal Mexican-Mestizo Women

Osteoporosis is characterized by low bone mineral density (BMD). One of the most important factors that influence BMD is the genetic contribution. The collagen type 1 alpha 1 (COL1A1) and the JAGGED (JAG1) have been investigated in relation to BMD. The aim of this study was to investigate the possible association between two single-nucleotide polymorphisms (SNPs) of COL1A1, their haplotypes, and one SNP of JAG1 with BMD in postmenopausal Mexican-Mestizo women. Seven hundred and fifty unrelated postmenopausal women were included. Risk factors were recorded and BMD was measured in lumbar spine, total hip, and femoral neck by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Two SNPs in COL1A1 (rs1800012 and rs1107946) and one in JAG1 (rs2273061) were studied. Real-time PCR allelic discrimination was used for genotyping. The differences between the means of the BMDs according to genotype were analyzed with covariance. Deviations from Hardy–Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r², and haplotype analysis of COL1A1 was conducted. Under a dominant model, the rs1800012 polymorphism of the COL1A1 showed an association with BMD of the lumbar spine (P = 0.021). In addition, analysis of the haplotype of COL1A1 showed that the G–G haplotype presented a higher BMD in lumbar spine. We did not find an association between the s1107946 and rs2273061 polymorphisms of the COL1A1 and JAG1, respectively. Our results suggest that the rs1800012 polymorphism of the COL1A1, in addition to one haplotype, were significantly associated with BMD variation in Mexican-Mestizo postmenopausal women.     

Cardiovascular Genetic Medicine: The Genetics of Coronary Heart Disease

Advances in genomic technologies have provided researchers with an unprecedented opportunity to identify genes that may contribute to the development of coronary heart disease. The power of these technologies lies in their ability to survey the entire genome in a nonbiased fashion to find genes and gene variants associated with coronary heart disease. This article reviews different genomic approaches for studying coronary heart disease and the clinical implications of using genetic information.     

血小板膜糖蛋白受体I b α Kozak序列基因多态性与缺血性脑血管病相关性的研究

目的研究GP I bαKozak序列基因多态性与缺血性脑血管病的相关性。方法本研究采用聚合链式反应对正常对照组228例和缺血性脑血管病组232例进行研究,对所得结果进行统计学处理,得出GP I bαKozak序列基因多态性与缺血性脑血管病的相关性。结果缺血性脑血管病组Kozak序列C等位基因(TC 33．4％, CC 4．3％)的比例达到37．7％。对照组C等位基因(TC 21．2％,CC 21．8％)的比例为23%,经卡方检验,两组比较, X2=17．378,df=1,P=0．03,具有显著性差异。Kozak序列C等位基因脑栓塞组21．6％;腔梗组28．1％;大面积梗塞组36．3％;对照组与脑栓塞组比较,X2=3．086,df=1,P=0．079,没有显著性差异。与腔梗组比较X2=1．854,df =1,P=0．173,没有显著性差异。与大面积梗塞组比较X2=4．293,df=1,P=0．038,有显著性差异。结论血小板膜糖蛋白受体I bαKozak序列基因多态性与缺血性脑血管病明显相关。     

Association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population

Objective To study the association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population. Methods XbaI and EcoRI polymorphisms of the apolipoprotein B (APOB) gene were genotyped by polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) method in 503 unrelated hypertensive patients and 490 healthy controls recruited from international collaborative study of cardiovascular disease in Asia (InterAsia). Results The difference in the genotypic distributions could be neglected across the groups. The prevalence of X allele in healthy controls (4.8%) was less frequent in Chinese, and there was no significant difference in the frequency of the X allele between cases (5.7%) and controls (P=0.38). The observed E- allele frequencies were closely similar among groups (5.9% in cases vs 5.0% in controls, P=0.39). Logitstic regression analyses revealed that the lack of association still persisted after adjustment of other environmental factors. Haplotype analysis showed that X-E was most frequent and no haplotype could significantly contribute to essential hypertension. Conclusion The APOB gene XbaI and EcoRI polymorphisms are not associated with essential hypertension in the Northern Chinese Han population. Future studies on single nucleotide polymorphisms in larger samples are needed to further investigate the possible contribution of the APOB gene to essential hypertension.     

Levels of 2-thiothiazolidine-4-carboxylic acid (TTCA) and effect modification of polymorphisms of glutathione-related genes in vulcanization workers in the southern Sweden rubber industries

Objectives Workers in the rubber industry are exposed to a complex mixture of hazardous substances and have increased risk of developing several diseases. However, there is no up to date survey examining the exposure in the Swedish rubber industry. One of the toxic compounds in the industry is carbon disulfide (CS₂), which is biotransformed to 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as a biomarker of CS₂ exposure, but there seem to exist inter- and intraindividual variability; which could partly be due to genetic variation. The aim of the study was to determine TTCA levels and the modifying effects of glutathione-related genes in a group of Swedish rubber workers. Methods Urine was collected from both exposed workers and controls during the last 4 h of the work shift. The level of TTCA in urine was analyzed by liquid chromatograpy tandem mass spectrometry. Genotyping of the single nucleotide polymorphisms GCLC-129, GCLM-588, GSTA1-52, GSTP1-105 and GSTP1-114 and deletions of GSTM1 and GSTT1 were performed with real-time PCR or ordinary PCR and subsequent agarose electrophoresis. Results The highest levels of TTCA were found among workers curing with salt bath, hot air, microwaves or fluid-bed, and lower levels were found among workers curing with injection and compression molding. Furthermore, with respect to GSTM1 and GSTT1 there were statistically significant differences in TTCA-levels between genotypes among exposed workers but not among controls. The other five polymorphisms had no impact on the TTCA levels. Conclusions The present study demonstrates relatively high levels of TTCA in urine from Swedish rubber workers. Polymorphisms in GSTM1 and GSTT1 modify the levels.     

The genetic polymorphism and expression profiles of NLRP3 inflammasome in patients with chronic myeloid leukemia

NLRP3 inflammasome has been recently reported as an important risk factor in the development of cancer. But the relationship between polymorphisms of NLRP3 inflammasome related genes and chronic myeloid leukemia (CML) is rarely reported. Therefore, the aim of the present study was to investigate the association of five genetic polymorphisms (NLRP3, IL-1β, IL-18, CARD8 and NF-κB) in 267 CML patients and 344 healthy controls. We found that the AT genotype of CARD8 (rs2043211) was significantly higher compared to TT genotype in high and intermediate risk CML patients. IL-1β (rs16944) polymorphism in early molecular response at 6?months was marginally different, with more GG and less AA genotype in BCR-ABL^IS >1% group. IL-18 (rs1946518) polymorphism was significantly different with more GG genotype in BCR-ABL^IS >1% group at 6?months. We also demonstrated that WBC count of newly diagnosed patients carrying AG genotype was significantly higher than that of GG or AA genotype of IL-1β (rs16944). The onset age of patients carrying ins/ins genotype of NF-κB (rs28362491) was significantly older than that of ins/del and del/del genotype. Moreover, IL-1β or NLRP3 mRNA expression was decreased and IL-18 mRNA expression was increased significantly in CML patients compared with controls. In conclusion, the genetic polymorphisms of NLRP3 inflammasome may be served as potential predictors for CML.     

NRAMP1基因DNA多态性与海南黎族人结核病易感性的研究

目的探讨自然抵抗相关巨噬细胞蛋白1(NRAMP1)基因D543N和3′UTR位点多态性与海南黎族人结核病易感性的关系。方法采用病例对照研究设计,共有130例肺结核病例和233例对照纳入本研究,用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析的方法检测入选人群NRAMP1基因中D543N和3′UTR位点的多态性,并对结核病相关危险因素进行问卷调查,进行单因素和基因频率的分析。结果对所有研究对象进行D543N和3′UTR两个多态性位点的基因分型,3′UTR-TGTG+/TGTG-和3′UTR-TGTG-/TGTG-基因型病例组频率显著高于对照组,OR值分别为5.531(2.649-11.549)和0.181(0.087-0.378);D543N位点各基因型频率在病例和对照组中的频率无显著性差异;同时对4个相关危险因素进行了单因素分析,结果性别、酗酒两个因素在病例组和对照组中有显著性差异,OR值(95%CI)分别为3.937(2.459-6.304)和2.435(1.507-3.937),在多因素分析中,调整了性别、吸烟、酗酒3个因素后,3′UTR-TGTG+/TGTG-和3′UTR-TGTG-/TGTG-基因型仍与肺结核显著相关,OR值(95%CI)分别为5.140(2.394-11.034)和4.929(2.769-8.775)。结论NRAMP1基因3′UTR位点多态性可能是海南黎族人结核病的易感因素,D543N位点多态性与海南黎族人结核病的发生无关。