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1.
背景与目的:CD44分子是众多肿瘤细胞的标志分子,其表达水平与肿瘤细胞的恶性程度有关。该研究探讨CD44基因中的单核苷酸多态性(single nucleotide polymorphism,SNP)位点与云南汉族人群宫颈癌和非小细胞肺癌(nonsmall cell lung cancer,NSCLC)易感性的相关性。方法:选取了CD44基因中的两个SNP位点rs13347和rs8193,采用TagMan基因分型的方法,分析这两个多态性位点在497例宫颈癌患者和500例健康对照个体以及483例NSCLC患者和471例健康对照个体中的分布特征,并分析CD44基因中的多态性位点与云南汉族人群宫颈癌和NSCLC的相关性。结果:rs13347和rs8193位点等位基因和基因型在宫颈癌组和对照组中的分布频率的差异无统计学意义(P>0.05)。而在NSCLC组和对照组的比较中:rs13347和rs8193位点等位基因在NSCLC组和对照组中的分布频率的差异有统计学意义(P=0.020和P=0.004);这两个位点基因型在NSCLC组和对照组中分布频率的差异有统计学意义(P=0.027和P=0.020);其中rs13347位点等位基因C在NSCLC组中的分布频率显著高于对照组,可能是NSCLC发生的风险因素(OR=1.250,95% CI:1.035~1.509),rs8193位点等位基因C在对照组中的分布频率显著高于NSCLC组,可能是NSCLC发生的保护性因素(OR=0.768,95%CI:0.641~0.921)。单倍型分析结果显示,rs13347C-rs8193T和rs13347T-rs8193C在NSCLC组和对照组中的分布频率差异有统计学意义(P=0.003和0.022);该结果说明单倍型rs13347C-rs8193T可能是云南汉族人群NSCLC发生的风险性因素(OR=1.316,95%CI:1.096~1.579)。结论:CD44基因中的两个SNP位点rs13347和rs8193可能与云南汉族人群宫颈癌发病风险无关,而可能与云南汉族人群NSCLC具有相关性。 相似文献
2.
6-Mercaptopurine (6-MP) is commonly used for treatment of acute lymphoblastic leukemia (ALL). The incidence of hematotoxicity caused by this drug is quite high in Asians even using a standard low dosage regimen. The present study was aimed to elucidate the impact of thiopurine S-methyltransferase (TPMT), a nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15), inosine triphosphatase (ITPA) and ATP Binding Cassette Subfamily C Member 4 (ABCC4) polymorphisms on hematotoxicity in pediatric patients who received a standard low starting dose of 6-MP. One hundred and sixty-nine pediatric patients were enrolled and their genotypes were determined. Patients who carried NUDT1513 and NUDT1512 genotypes were at a 10–15 fold higher risk of severe neutropenia than those of the wild-type during the early months of the maintenance phase. Risk of neutropenia was not significantly increased in patients with other NUDT15 variants as well as in patients with TPMT, ITPA or ABCC4 variants. These results suggest that NUDT15 polymorphisms particularly, NUDT1513 and NUDT1512, play major roles in 6-MP-induced severe hematotoxicity even when using a standard low dosage of 6-MP and genotyping of these variants is necessary in order to obtain precise tolerance doses and avoid severe hematotoxicity in pediatric patients. 相似文献
3.
4.
S. D. ROBINSON† C. A. LUDLAM‡ N. A. BOON† D. E. NEWBY† 《Journal of thrombosis and haemostasis》2006,4(10):2262-2269
OBJECTIVES: To determine if polymorphisms of the tissue plasminogen activator (t-PA) gene influence acute endogenous t-PA release in patients with coronary heart disease (CHD). METHODS: Forearm blood flow and plasma t-PA concentrations were measured in response to intra-brachial infusion of substance P and sodium nitroprusside in 96 patients with stable CHD. Genotyping was performed using a Taqman polymerase chain reaction assay specifically designed to detect the polymorphisms of interest: (i) Alu-repeat insertion/deletion sequence; (ii) C-->T substitution in an upstream enhancer region (-7351 C/T); (iii) T-->C in exon 6 (20 099 T/C); and (iv) T-->A (27 445 T/A) in intron 10. RESULTS: Substance P and sodium nitroprusside caused dose-dependent increases in forearm blood flow in all patients (P < 0.001 for all) that were independent of the four genetic polymorphisms. Similarly, there were no differences in basal plasma t-PA antigen concentrations or net t-PA release between genotypes. Compared to non-smokers, smokers exhibited impaired substance P-induced vasodilatation (P < 0.001) and t-PA release (P = 0.05). CONCLUSIONS: Despite confirming our previous findings in cigarette smokers, we have found no effect of polymorphisms of the t-PA gene on two complementary aspects of endothelial function. We conclude that genetic variation of the t-PA locus is unlikely to have a major influence on acute t-PA release in subjects with established CHD. 相似文献
5.
6.
湖南省乙肝病毒基因型分布及临床意义 总被引:1,自引:0,他引:1
目的 :研究湖南省乙肝病毒 (HBV)基因型分布及临床意义。方法 :选择湖南省HBVDNA阳性慢性乙肝病人共 185例 ,其中病毒携带者 (ASC) 4 2例 ,慢性轻、中度肝炎 (CH) 38例 ,重型肝炎 (FHF) 80例 (伴有肝硬化者 4 9例 ) ,肝细胞癌 (HCC) 2 5例 ,采用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)方法检测HBV基因型。结果 :基因型B136例 (73.5 % ) ,基因型C 4 9例 (2 6 .5 % )。基因型B在FHF中占绝对优势 (83.7% ) ,其次为HCC(76 % ) ,与ASC(5 7.1% )比较 ,差异有显著性 (P <0 .0 1)。与基因型B相比 ,基因型C在垂直传播感染者中多见 (38.8%与 13.2 % ,P <0 .0 0 1) ;HBeAg阳性率明显增高 (5 7.1%与 30 .9% ,P <0 .0 0 1) ;抗HBe阳性率明显下降 (36 .9%与 6 6 .2 % ,P <0 .0 0 1)。与基因型C相比 ,基因型B感染者ALT水平明显增高 (2 6 4 .5± 2 5 6 .5与 10 0± 12 0 .6 ,P <0 .0 0 1)。结论 :湖南省存在乙肝病毒基因型B和基因型C ;基因型B为优势基因型并与肝脏疾病活动性相关 ,基因型C与母婴垂直传播感染有关 相似文献
7.
Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease. 总被引:6,自引:0,他引:6
C P Day 《Liver international》2006,26(9):1021-1028
While the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome will have steatosis, only a minority will ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of fibrosis. For ALD, the dose and pattern of alcohol intake, along with obesity are the most important environmental factors determining disease risk. For NAFLD, dietary saturated fat and antioxidant intake and small bowel bacterial overgrowth may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis. 相似文献
8.
Malcolm D. McGinnis Roger V. Lebo David L. Quinn Malcolm J. Simons 《American journal of medical genetics. Part A》1994,52(4):438-444
A 438 basepair intron 1 sequence adjacent to exon 2 in the human major histocompatibility complex DQA1 gene defined 16 allelic variants in 69 individuals from wide ethnic backgrounds. In contrast, the most variable coding region spanned by the 247 basepair exon 2 defined 11 allelic variants. Our phylogenetic human intron 1 tree derived by the Bootstrap algorithm reflects the same relative allelic relationships as the reported DQA1 exon 2 tree [Gyllensten and Erlich, Hum Immunol 36:1–10, 1989]. Thus 3′ DQA1 intron 1 and exon 2 have cosegregated since divergence of the human races. Comparison of human alleles to a Rhesus monkey DQA1 first intron sequence found only 10 nucleotide substitutions unique to Rhesus, with the other 428 positions (98%) found in at least one human allele. This high degree of homology reflects the evolutionary stability of intron sequences since these two species diverged over 20 million years ago. Because more intron 1 alleles exist than exon 2 alleles, these polymorphic introns can be used to improve tissue typing for transplantation, paternity testing, and forensics and to derive more complete phylogenetic trees. These results suggest that introns represent a previously underutilized polymorphic resource. © 1994 Wiley-Liss, Inc. 相似文献
9.
V. Haufroid P. Wallemacq V. VanKerckhove L. Elens M. De Meyer D. C. Eddour J. Malaise D. Lison M. Mourad 《American journal of transplantation》2006,6(11):2706-2713
Genetic polymorphisms in biotransformation enzyme CYP3A5 (6986G > A, CYP3A5*3; 14690A > G, CYP3A5*6) and drug transporter ABCB1 (1236C > T; 2677G > T/A; 3435C > T) are known to influence tacrolimus (Tac) dose requirements and trough blood levels in stable transplant patients. In a group of 19 volunteers selected with relevant genotypes among a list of 221 adult renal transplant candidates, we evaluated whether consideration of CYP3A5 and ABCB1 genetic polymorphisms could explain the interindividual variability in Tac pharmacokinetics after the first administration of a standard dose (0.1 mg/kg body weight twice a day). Lower area under the time versus blood concentration curves (AUC) or lower trough concentrations were observed among CYP3A5 expressors (n = 9) than among nonexpressors (n = 10) using two different analytical methods for Tac determination (liquid chromatography with tandem mass spectrometry (LC-MS/MS) and immunoassay). The median AUC(0-infinity) was 2.6- and 2.1-fold higher in nonexpressors for LC-MS/MS and immunologic methods, respectively. No difference was observed in Tac pharmacokinetic parameters in relation to ABCB1 polymorphisms. In conclusion, our study confirms the very significant effect of CYP3A5 polymorphism early after the first administration of Tac. It also provides a strong argument for a doubling of the loading dose in patients early identified a priori on the transplantation list as possessing at least one CYP3A5*1 allele. 相似文献
10.
D. Galimberti D. Scalabrini C. Fenoglio C. Comi M. De Riz E. Venturelli C. Lovati C. Mariani F. Monaco N. Bresolin E. Scarpini 《European journal of neurology》2007,14(2):162-167
CXCL10 (interferon- γ -inducible protein-10) levels are increased in cerebrospinal fluid of multiple sclerosis (MS) patients with symptomatic attacks of inflammatory demyelination, supporting a role for this molecule in MS pathogenesis. Two hundred and twenty-six patients with MS and 235 controls were genotyped for G → C and T → C single nucleotide polymorphisms (SNPs) in exon 4 of CXCL10 gene. Haplotypes were tested for association and correlated with clinical variables. The two SNPs studied were in complete linkage disequilibrium. None of the determined haplotypes was associated with MS. However, carriers of the GGTT haplotype (defined as wild type, according to the sequence in National Centre for Biotechnology Information (NCBI) database) had a significantly lower progression index than non-carriers ( P = 0.016). Furthermore, amongst patients who had an initial relapsing remitting (RR) course of the disease, the time between onset and second episode was significantly longer in GGTT carriers ( P = 0.021). Considering secondary progressive (SP)–MS patients, the time between the initial RR form and the subsequent worsening to SP was longer in this group ( P = 0.08). Therefore, the GGTT haplotype of the CXCL10 gene is not a susceptibility factor for the development of MS, but is probably to influence the course of MS, possibly contributing to slow down the progression of the disease. 相似文献