Pharmacogenetics最新文献_第7页

Prediction of successful weight reduction under sibutramine therapy. 西布曲明治疗下成功减肥的预测。

Pharmacogenetics Pub Date : 2004-06-01 DOI: 10.1097/00008571-200406000-00008

Leonardo Sahelijo, David A Katz, Brian B Spear

引用次数: 12

Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity. HLA B*5701基因分型预防阿巴卡韦过敏的成本-效果分析。

Pharmacogenetics Pub Date : 2004-06-01 DOI: 10.1097/00008571-200406000-00002

Dyfrig A Hughes, F Javier Vilar, Charlotte C Ward, Ana Alfirevic, B Kevin Park, Munir Pirmohamed

{"title":"Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity.","authors":"Dyfrig A Hughes, F Javier Vilar, Charlotte C Ward, Ana Alfirevic, B Kevin Park, Munir Pirmohamed","doi":"10.1097/00008571-200406000-00002","DOIUrl":"https://doi.org/10.1097/00008571-200406000-00002","url":null,"abstract":"OBJECTIVE Abacavir, a human immunodeficiency virus-1 (HIV-1) nucleoside-analogue reverse transcriptase inhibitor, causes severe hypersensitivity in 4-8% of patients. HLA B*5701 is a known genetic risk factor for abacavir hypersensitivity in Caucasians. Our aim was to confirm the presence of this genetic factor in our patients, and to determine whether genotyping for HLA B*5701 would be a cost-effective use of healthcare resources. METHODS Patients with and without abacavir hypersensitivity were identified from a UK HIV clinic. Patients were genotyped for HLA B*5701, and pooled data used for calculation of test characteristics. The cost-effectiveness analysis incorporated the cost of testing, cost of treating abacavir hypersensitivity, and the cost and selection of alternative antiretroviral regimens. A probabilistic decision analytic model (comparing testing versus no testing) was formulated and Monte Carlo simulations performed. RESULTS Of the abacavir hypersensitive patients, six (46%) were HLA B*5701 positive, compared to five (10%) of the non-hypersensitive patients (odds ratio 7.9 [95% confidence intervals 1.5-41.4], P = 0.006). Pooling of our data on HLA B*5701 with published data resulted in a pooled odds ratio of 29 (95% CI 6.4-132.3; P < 0.0001). The cost-effectiveness model demonstrated that depending on the choice of comparator, routine testing for HLA B*5701 ranged from being a dominant strategy (less expensive and more beneficial than not testing) to an incremental cost-effectiveness ratio (versus no testing) of Euro 22,811 per hypersensitivity reaction avoided. CONCLUSIONS Abacavir hypersensitivity is associated with HLA B*5701, and pre-prescription pharmacogenetic testing for this appears to be a cost-effective use of healthcare resources.","PeriodicalId":19917,"journal":{"name":"Pharmacogenetics","volume":"14 6","pages":"335-42"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00008571-200406000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24609822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 270

Bringing genomics to the bedside: a cost-effective pharmacogenomic test? 将基因组学带到床边:一种具有成本效益的药物基因组学测试?

Pharmacogenetics Pub Date : 2004-06-01 DOI: 10.1097/00008571-200406000-00001

David L Veenstra

引用次数: 6

Functional responses of human beta1 adrenoceptors with defined haplotypes for the common 389R>G and 49S>G polymorphisms. 389R>G和49S>G常见多态性对确定单倍型的人β 1肾上腺素受体的功能反应

Pharmacogenetics Pub Date : 2004-06-01 DOI: 10.1097/00008571-200406000-00003

Alastair Sandilands, Giles Yeo, Morris J Brown, Kevin M O'Shaughnessy

{"title":"Functional responses of human beta1 adrenoceptors with defined haplotypes for the common 389R>G and 49S>G polymorphisms.","authors":"Alastair Sandilands, Giles Yeo, Morris J Brown, Kevin M O'Shaughnessy","doi":"10.1097/00008571-200406000-00003","DOIUrl":"https://doi.org/10.1097/00008571-200406000-00003","url":null,"abstract":"Objectives: The human beta1-adrenoceptor (beta1-AR) is an important therapeutic target for cardiovascular diseases and has two common functional polymorphisms (49S>G and 389R>G). These polymorphisms have only been studied in isolation, however, and not in the context of the four haplotypes (SR, SG, GR and GG) that exist in native beta1-ARs.Methods: To address this, the function of each of the receptor haplotypes was studied in HEK 293 cells stably transfected with appropriately modified human beta1-adrenoceptor cDNA sequence.Results: The affinity for the beta-adrenoceptor ligand, [125I]-cyanopindolol, was not significantly different across the haplotypes, but a high affinity state for the beta1-AR could only be demonstrated for receptors carrying the 389R substitution. Both basal (GR 36.3 +/- 2.9* vs. SR 16.5 0 +/- 3.6 and GG 31.7 +/- 1.4* vs. SG 15.6 +/- 1.5 pmol/mg protein; *P < 0.001) and maximal (GR 163 +/- 7.6 vs. SR 124 +/- 8.1* and GG 75.0 +/- 1.0 vs. SG 52.4 +/- 1.1* pmol/mg protein; *P < 0.001) isoprenaline-evoked cAMP production was significantly affected by both substitutions. Incubation with isoprenaline (10 microm for 30 min or 20 h) caused increased down-regulation of beta1-ARs in cells expressing GG and GR haplotypes (at 20 h percentage fall respectively -28.1 +/- 5.2 and -38.2 +/- 3.0).Conclusions: These data highlight important functional differences between the common beta1-AR haplotypes and the need for consideration of haplotypes and not individual genotypes in determining the in-vivo role of these polymorphisms within this important drug target.","PeriodicalId":19917,"journal":{"name":"Pharmacogenetics","volume":"14 6","pages":"343-9"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00008571-200406000-00003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24609823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 41

Functional polymorphisms of UDP-glucuronosyltransferases 1A1, 1A6 and 1A8 are not involved in chronic pancreatitis. udp -葡萄糖醛基转移酶1A1、1A6和1A8的功能多态性与慢性胰腺炎无关。

Pharmacogenetics Pub Date : 2004-06-01 DOI: 10.1097/00008571-200406000-00004

Mariette Verlaan, René H M te Morsche, Akos Pap, Robert J F Laheij, Jan B M J Jansen, Wilbert H M Peters, Joost P H Drenth

{"title":"Functional polymorphisms of UDP-glucuronosyltransferases 1A1, 1A6 and 1A8 are not involved in chronic pancreatitis.","authors":"Mariette Verlaan, René H M te Morsche, Akos Pap, Robert J F Laheij, Jan B M J Jansen, Wilbert H M Peters, Joost P H Drenth","doi":"10.1097/00008571-200406000-00004","DOIUrl":"https://doi.org/10.1097/00008571-200406000-00004","url":null,"abstract":"Objectives: Chronic pancreatitis (CP) is associated with alcohol abuse, smoking and other dietary or environmental factors. UDP-glucuronosyltransferases (UGTs) are phase II detoxifying enzymes responsible for glucuronidation of various exogenous and endogenous compounds. Genetic variations, resulting in variable rates of glucuronidation, are of toxicological and physiological importance and are frequently associated with diseases. Recently, a genetic polymorphism in UGT1A7 was possibly associated with an increased risk for CP. We investigated whether polymorphisms in the genes for UGT1A1, UGT1A6 and UGT1A8 modified the risk for CP.Methods: DNA samples were obtained from 258 adult CP patients with alcoholic (n = 153), hereditary (n = 25) or idiopathic (n = 80) origin. DNA from 140 healthy controls was analyzed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in UGTs were determined by PCR, eventually followed by restriction-fragment-length-polymorphism analyses in all subjects.Results: The distribution of the various alleles of UGT1A1, UGT1A6 and UGT1A8 did not differ between CP patients and healthy controls.Conclusion: These data suggest that genetic polymorphisms in UGT1A1, UGT1A6 and in UGT1A8 do not predispose to the development of CP in Caucasians.","PeriodicalId":19917,"journal":{"name":"Pharmacogenetics","volume":"14 6","pages":"351-7"},"PeriodicalIF":0.0,"publicationDate":"2004-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00008571-200406000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24609824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene (MDR1, ABCB1). 人胎盘p -糖蛋白的可变表达及其与多药耐药1基因(MDR1, ABCB1)突变的关系

Pharmacogenetics Pub Date : 2004-05-01 DOI: 10.1097/00008571-200405000-00006

Monika Hitzl, Elke Schaeffeler, Berthold Hocher, Torsten Slowinski, Horst Halle, Michel Eichelbaum, Peter Kaufmann, Peter Fritz, Martin F Fromm, Matthias Schwab

{"title":"Variable expression of P-glycoprotein in the human placenta and its association with mutations of the multidrug resistance 1 gene (MDR1, ABCB1).","authors":"Monika Hitzl, Elke Schaeffeler, Berthold Hocher, Torsten Slowinski, Horst Halle, Michel Eichelbaum, Peter Kaufmann, Peter Fritz, Martin F Fromm, Matthias Schwab","doi":"10.1097/00008571-200405000-00006","DOIUrl":"https://doi.org/10.1097/00008571-200405000-00006","url":null,"abstract":"The MDR1 gene product P-glycoprotein in the human placenta is important for protecting the fetus from unintended, harmful drug exposure, but also for limiting the access of therapeutic drugs to the fetus after maternal drug intake. A polymorphism in exon 26 of the MDR1 gene (C3435T) has previously been shown to be associated with reduced P-glycoprotein expression in the small intestine, kidney and lymphocytes. In the present study, we examined systematically whether MDR1 polymorphisms also have an impact on P-glycoprotein expression in the human placenta. MDR1 mRNA and P-glycoprotein were analysed in 73 full-term human placentas of Caucasians, as well as respective MDR1 genotypes/haplotypes, for the C3435T and G2677T/A polymorphisms of mothers and infants. MDR1 mRNA levels were not different between these genotype groups. However, P-glycoprotein expression was significantly lower when both mother and infant were homozygous for the 3435T allele (TT/tt) compared to maternal and fetal homozygotes for the C-allele (0.40 +/- 0.18 a.u. for TT/tt versus 0.66 +/- 0.30 a.u. for CC/cc, P = 0.01). Moreover, placentas from mothers carrying both polymorphisms (3435T and 2677T; TT/TT) also had a significantly lower P-glycoprotein expression (0.31 +/- 0.12 a.u.) compared to placentas of wild-type individuals (CC/GG, 0.71 +/- 0.31 a.u., P = 0.02). Taken together, the MDR1 polymorphisms C3435T and G2677T are associated with altered P-glycoprotein expression in the human placenta, and may have clinical consequences due to genetically determined, variable drug exposure of the fetus.","PeriodicalId":19917,"journal":{"name":"Pharmacogenetics","volume":"14 5","pages":"309-18"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00008571-200405000-00006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24495168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 112

Investigation of the association between 5-HT3A receptor gene polymorphisms and efficiency of antiemetic treatment with 5-HT3 receptor antagonists. 5-HT3A受体基因多态性与5-HT3受体拮抗剂止吐效果的关系研究

Pharmacogenetics Pub Date : 2004-05-01 DOI: 10.1097/00008571-200405000-00001

Rolf Kaiser, Pierre-Benoit Tremblay, Orhan Sezer, Kurt Possinger, Ivar Roots, Jürgen Brockmöller

{"title":"Investigation of the association between 5-HT3A receptor gene polymorphisms and efficiency of antiemetic treatment with 5-HT3 receptor antagonists.","authors":"Rolf Kaiser, Pierre-Benoit Tremblay, Orhan Sezer, Kurt Possinger, Ivar Roots, Jürgen Brockmöller","doi":"10.1097/00008571-200405000-00001","DOIUrl":"https://doi.org/10.1097/00008571-200405000-00001","url":null,"abstract":"Objectives: Acute cytostatic drug induced nausea and vomiting is provoked by a release of endogenous serotonin that mediates its effect by binding to the 5-hydroxytryptamine type 3 (5-HT3) receptors. The most effective antiemetic drugs are the 5-HT3 receptor antagonists. Nevertheless about 30% of the patients do not respond satisfactorily. Five 5-HT3 receptor genes (5-HT(3A-E)) with high sequence homology have been identified. Two subunits, the 5-HT3A and 5-HT3B are expressed in anatomical structures known to be involved in the mechanism of acute cytostatic drug induced emesis.Methods: We included 242 cancer patients at their first day of chemotherapy to investigate the influence of genetic polymorphisms of the 5-HT3A receptor gene on the intensity of nausea and vomiting which was documented using standardized interviews and visual analog scales.Results: Sequencing of the entire 5-HT3A receptor gene of all patients revealed 21 polymorphisms, two of them were amino acid substitutions (Ala33Thr, Met257Ile). Linkage disequilibrium analysis revealed that 15 polymorphisms of the 5-HT3A receptor gene are partially linked to each other. However, none of the haplotypes was significantly associated with the intensity of cytostatic induced nausea and vomiting.Conclusion: Polymorphisms and haplotype analysis of the 5-HT3A receptor gene may not serve as a pharmacogenetic predictor of the antiemetic treatment with 5-HT3 receptor antagonists in cancer patients.","PeriodicalId":19917,"journal":{"name":"Pharmacogenetics","volume":"14 5","pages":"271-8"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00008571-200405000-00001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24495239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 59

Impact of CYP2D6 intermediate metabolizer alleles on single-dose desipramine pharmacokinetics. CYP2D6中间代谢等位基因对单剂量地西帕明药代动力学的影响。

Pharmacogenetics Pub Date : 2004-05-01 DOI: 10.1097/00008571-200405000-00002

Katherine D Furman, David R Grimm, Toby Mueller, Rhonda R Holley-Shanks, Richard J Bertz, Laura A Williams, Brian B Spear, David A Katz

{"title":"Impact of CYP2D6 intermediate metabolizer alleles on single-dose desipramine pharmacokinetics.","authors":"Katherine D Furman, David R Grimm, Toby Mueller, Rhonda R Holley-Shanks, Richard J Bertz, Laura A Williams, Brian B Spear, David A Katz","doi":"10.1097/00008571-200405000-00002","DOIUrl":"https://doi.org/10.1097/00008571-200405000-00002","url":null,"abstract":"This study utilized cytochrome P450 2D6 (CYP2D6) genotypes to explain variability of desipramine pharmacokinetics in a cohort of non-poor metabolizer individuals. In an interaction study utilizing desipramine as a probe, genotyping for the CYP2D6*3, *4, *5 and *6 alleles was used to screen out CYP2D6 poor metabolizers. Individuals were categorized according to these and additional alleles (CYP2D6*2, *9, *10, *17, *41 and x2). Genotypes of individuals heterozygous for two or three of *2, *17 and *41 alleles were confirmed by molecular haplotyping. Pharmacokinetic parameters of desipramine were analysed according to CYP2D6 category. Molecular haplotyping was necessary to definitively categorize four of 16 individuals. A subject who had unusually high plasma elimination half-time, exposure and metabolic ratios carried an intermediate metabolizer (IM) *9 allele in combination with a non-functional allele. This combination has a population frequency of less than 1 : 200. Individuals with *1/*1, *1/*2 and *2/*2 genotypes had lower than average plasma elimination half-time, exposure and metabolic ratios. For desipramine, additional genotyping of CYP2D6 IM alleles helped define subgroups of the CYP2D6-positive cohort. This suggests that genotyping for IM alleles will aid in interpretation of clinical trials involving CYP2D6 substrates. Due to the diversity of IM alleles, molecular haplotyping may be necessary to fully characterize CYP2D6 genotype-phenotype relationships.","PeriodicalId":19917,"journal":{"name":"Pharmacogenetics","volume":"14 5","pages":"279-84"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00008571-200405000-00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24495241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 35

A novel polymorphism in the promoter region of human UGT1A9 gene (UGT1A9*22) and its effects on the transcriptional activity. 人UGT1A9基因启动子区(UGT1A9*22)的新多态性及其对转录活性的影响

Pharmacogenetics Pub Date : 2004-05-01 DOI: 10.1097/00008571-200405000-00008

Hiroyuki Yamanaka, Miki Nakajima, Miki Katoh, Yusuke Hara, Osamu Tachibana, Junkoh Yamashita, Howard L McLeod, Tsuyoshi Yokoi

{"title":"A novel polymorphism in the promoter region of human UGT1A9 gene (UGT1A9*22) and its effects on the transcriptional activity.","authors":"Hiroyuki Yamanaka, Miki Nakajima, Miki Katoh, Yusuke Hara, Osamu Tachibana, Junkoh Yamashita, Howard L McLeod, Tsuyoshi Yokoi","doi":"10.1097/00008571-200405000-00008","DOIUrl":"https://doi.org/10.1097/00008571-200405000-00008","url":null,"abstract":"The human UDP-glucuronosyltransferase, UGT1A9, catalyses glucuronidations of various endobiotics and xenobiotics. In the present study, all exons, exon-intron junctions, and the 5'-flanking region (-273 bp) of the UGT1A9 gene in a Japanese subject were sequenced. One base insertion of thymidine in a promoter region of the UGT1A9 gene resulting in A(T)10AT was identified compared to the reference sequence of AF297093 (A(T)9AT). The allele was termed UGT1A9*22. A polymerase chain reaction-single strand conformation polymorphism method was developed to genotype the allele. The allele frequencies of the mutation in 87 Japanese, 50 Caucasian and 50 African-American subjects were 60%, 39% and 44%, respectively. The significance of the polymorphism was investigated by the construction of luciferase reporter plasmids containing 170 bp of the 5'-flanking region of the gene transfected into human hepatoma HepG2 cells. The luciferase activity of the promoter construct containing the A(T)10AT sequence was 2.6-fold higher than that of the construct containing the A(T)9AT sequence. In conclusion, the mutant allele with one base insertion in the promoter region of the UGT1A9 gene would alter the level of enzyme expression and the metabolism of those drugs that are substrates of UGT1A9.","PeriodicalId":19917,"journal":{"name":"Pharmacogenetics","volume":"14 5","pages":"329-32"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00008571-200405000-00008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24495170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 124

Glutathione-S-transferase M1, M3, P1 and T1 polymorphisms and severity of lung disease in children with cystic fibrosis. 囊性纤维化儿童谷胱甘肽s转移酶M1、M3、P1和T1多态性与肺部疾病严重程度的关系

Pharmacogenetics Pub Date : 2004-05-01 DOI: 10.1097/00008571-200405000-00004

Cyril Flamant, Alexandra Henrion-Caude, Pierre-Yves Boëlle, François Brémont, Jacques Brouard, Bertrand Delaisi, Jean-François Duhamel, Christophe Marguet, Michel Roussey, Marie-Claude Miesch, Michèle Boulé, Richard C Strange, Annick Clement

{"title":"Glutathione-S-transferase M1, M3, P1 and T1 polymorphisms and severity of lung disease in children with cystic fibrosis.","authors":"Cyril Flamant, Alexandra Henrion-Caude, Pierre-Yves Boëlle, François Brémont, Jacques Brouard, Bertrand Delaisi, Jean-François Duhamel, Christophe Marguet, Michel Roussey, Marie-Claude Miesch, Michèle Boulé, Richard C Strange, Annick Clement","doi":"10.1097/00008571-200405000-00004","DOIUrl":"https://doi.org/10.1097/00008571-200405000-00004","url":null,"abstract":"Objectives: Progression and severity of lung disease differs markedly and early between patients with cystic fibrosis (CF). We investigated the hypothesis that polymorphisms in the detoxifying enzymes glutathione-S-transferase (GST) could influence phenotypic presentation of lung disease in CF.Methods: Genotypes for GSTM1, GSTM3, GSTP1 and GSTT1 were determined in a cohort of 146 children with CF by PCR-based methods. Pulmonary function, assessed by spirometric measures of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), was analysed in children at the age of 9.Results: No association between spirometric measurements, and GSTM1, GSTP1 or GSTT1 genotypes was found. As compared with patients homozygous for GSTM3*A allele, CF children carrying the GSTM3*B allele displayed a significant better lung function, assessed by both mean values of FEV1 and of FVC (respectively P = 0.01 and P = 0.002). These correlations remained significant after adjustment for potential confounding factors (respectively adjusted P = 0.008 and P = 0.002) and also in subgroups of CF patients who carry the deltaF508 CFTR mutation. Haplotype analysis of GSTM3 in combination with GSTM1 indicated that the positive impact of GSTM3*B allele on pulmonary performances was barely influenced by the GSTM1 genotypes of CF children.Conclusions: These data provide the first evidence suggesting that polymorphism of the GSTM3 gene contributes to clinical severity in CF, which may have prognostic significance and could prompt to start a more targeted therapy in young patients with CF.","PeriodicalId":19917,"journal":{"name":"Pharmacogenetics","volume":"14 5","pages":"295-301"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00008571-200405000-00004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24495243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 45