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Biomedical subjects

Carmen Martínez

Publications and source records attributed to Carmen Martínez.

At least 19 recordsLinked to original sources
PubMed2006

Myocyte enhancing factor-2A in Alzheimer's disease: genetic analysis and association with MEF2A-polymorphisms.

Polymorphisms at different genes have been proposed as determinants of the risk for developing late-onset Alzheimer's disease (LOAD). Among the several candidate genes are those that encode proteins involved in neuronal degeneration/survival. Studies of primary neuronal cultures supported that members of the myocyte enhancing factor-2 (MEF2) family of transcription factors have an anti-apoptotic effect, regulating the expression of proteins involved in neuronal survival and differentiation. We analysed the MEF2A gene in a total of 357 patients (mean age 72 years, range 60-97 years). Among others, a Pro279Leu in exon 8 and a polyglutamine (CAG) repeat polymorphisms in exon 12 were found. These variants were also genotyped in 495 healthy controls (>50 years old), and the frequencies were statistically compared. Eight patients were 279L (six P/L and two L/L), compared to only one control (2% vs. 0.2%; p=0.004, OR=11.32). There was a significantly higher frequency of 279L-carriers among APOE epsilon4+ (7/154=4.5%), compared to epsilon4- (1/203) (p=0.02). In conclusion, our work suggests that the variation at the MEF2A gene could be involved in the risk of developing LOAD. Because MEF2 has been related with neuronal survival, and the 279L allele has been related with a reduction in the transcriptional activation activity of MEF2A, the effect of this allele could be mediated through a down-regulation of antiapoptotic genes.

Aged↗
PubMed2006

Physical activity and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition Cohort.

Research conducted predominantly in male populations on physical activity and lung cancer has yielded inconsistent results. We examined this relationship among 416,277 men and women from the European Prospective Investigation into Cancer and Nutrition (EPIC). Detailed information on recent recreational, household and occupational physical activity, smoking habits and diet was assessed at baseline between 1992 and 2000. Relative risks (RR) were estimated using Cox regression. During 6.3 years of follow-up we identified 607 men and 476 women with incident lung cancer. We did not observe an inverse association between recent occupational, recreational or household physical activity and lung cancer risk in either males or females. However, we found some reduction in lung cancer risk associated with sports in males (adjusted RR = 0.71; 95% confidence interval 0.50-0.98; highest tertile vs. inactive group), cycling (RR = 0.73; 0.54-0.99) in females and non-occupational vigorous physical activity. For occupational physical activity, lung cancer risk was increased for unemployed men (adjusted RR = 1.57; 1.20-2.05) and men with standing occupations (RR = 1.35; 1.02-1.79) compared with sitting professions. There was no evidence of heterogeneity of physical activity associations across countries, or across any of the considered cofactors. For some histologic subtypes suggestive sex-specific reductions, limited by subgroup sizes, were observed, especially with vigorous physical activity. In total, our study shows no consistent protective associations of physical activity with lung cancer risk. It can be assumed that the elevated risks found for occupational physical activity are not produced mechanistically by physical activity itself but rather reflect exposure to occupation-related lung cancer risk factors.

Adult↗
PubMed2006

Case-control comparison of at-home to total hospital care for autologous stem-cell transplantation for hematologic malignancies.

PURPOSE: One of the most significant limitations of at-home autologous stem-cell transplantation (ASCT) is the necessity for hospital readmission. We developed an at-home ASCT program in which prophylactic ceftriaxone and treatment of febrile neutropenia with piperacillin and tazobactam was introduced to minimize the readmission rate. PATIENTS AND METHODS: Between November 2000 and February 2005, 178 consecutive patients underwent ASCT for a hematologic malignancy. Of these, 50 patients fulfilled the requirements for at-home ASCT. Results were compared with those observed in a control group of 50 patients individually matched to the group of patients treated at home for age, sex, diagnosis, stage of disease, conditioning, and source of stem cells. RESULTS: Febrile neutropenia occurred in fewer patients in the at-home group as compared with the hospitalized group (76% v 96%: P = .008), and duration of fever was also shorter in the at-home group (median, 2 and 6 days, respectively; range, 1 to 11 and 1 to 20 days, respectively; P = .00003). Hospital readmission in the at-home group was required in only four cases (8%). This resulted in a reduction of 18.6 days of hospitalization per patient. Likewise, total median charges were approximately half in the at-home group as compared with the in-hospital group (3,345 euro v 6,250 euro, respectively; P < .00001). CONCLUSION: Results of at-home ASCT with prophylactic administration of ceftriaxone and domiciliary treatment of febrile neutropenia with piperacillin and tazobactam are highly satisfactory and significantly cheaper compared with those obtained with conventional in-hospital ASCT.

Adult↗
PubMed2006

CYP2C19 polymorphism and risk for essential tremor.

Many patients with essential tremor (ET) develop acute adverse effects to primidone. We investigated the association between CYP2C19 polymorphism (possibly related to primidone metabolism) and the risk for developing essential ET and acute adverse effects to primidone. Leukocytary DNA from 200 ET patients and 300 healthy controls was studied for the genotype CYP2C19 and the occurrence of CYP2C19 allelic variants by using allele-specific PCR amplification and Sma I and BamH I RFLP analyses. The frequencies of the genotype CYP2C19*1/CYP2C19*2 and of the allelic variant CYP2C19*2 were significantly higher in ET patients than in controls. The mean age at onset of ET did not differ significantly between patients with genotypes CYP2C19*1/CYP2C19*2andCYP2C19*1/CYP2C19*1. The frequencies of the genotype CYP2C19*1/CYP2C19*2 and the allelic variant CYP2C19*2 were similar in ET patients who developed acute adverse effects to primidone, in those who tolerated primidone and in controls; the frequencies were also similar in patients with head, voice, tongue and chin tremor compared with controls. These results suggest that heterozygosis CYP2C19*1/CYP2C19*2 is associated with the risk for ET, but not with the age at onset of ET, the presentation of acute side effects of primidone, or the existence of head, voice, tongue or chin tremor.

Adult↗
PubMed2006

Clinical factors influencing T-cell receptor excision circle (TRECs) counts following allogeneic stem cell transplantation in adults.

To ascertain the clinical factors involved in T-cell reconstitution after allogeneic stem cell transplantation (SCT), we evaluated serial assessments of lymphocyte subsets by flow cytometry and TRECs levels by quantitative PCR in 83 adult patients. Patient age >25 years, unrelated donor, CMV infection and acute graft-versus-host disease (GVHD) adversely affected CD3(+) and CD8(+) T-cell recovery after SCT (p < 0.05). TRECs were low or undetectable during the first months after transplant and progressively increased thereafter. However, median TRECs of patients did never achieve normal values compared to healthy donors (median follow-up 9 months, range 2-42). Presence and severity of chronic GVHD significantly affected TRECs counts: patients with chronic GVHD had lower TRECs than patients without GVHD at 9, 12 and 24 months after SCT (p = 0.002, p = 0.022, p = 0.015). Patients with limited chronic GVHD had higher TRECs compared to patients with extensive GVHD (p = 0.018). No relationship was observed between fungal or bacterial infections and TRECs. Nonetheless, CMV infection was associated with lower TRECs (p = 0.032). Our data support the concept that adult thymus contributes with a slow but continuous production of thymic T cells to immune reconstitution after SCT. Chronic GVHD is the main factor associated to a delay in TRECs counts recovery.

Adult↗
PubMed2006

Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene.

AIM: To analyse the role of two common polymorphisms in genes coding for histamine metabolising enzymes as it relates to the risk to develop ulcerative colitis (UC) and the clinical course of these patients. METHODS: A cohort of 229 unrelated patients with UC recruited from a single centre and 261 healthy volunteers were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N-methyltransferase (HNMT) and diamine oxidase (ABP1) enzymes, respectively, by amplification-restriction procedures. All patients were phenotyped and followed up for at least 2 years (mean time 11 years). RESULTS: There were no significant differences in the distribution of ABP1 alleles between ulcerative colitis patients and healthy individuals [OR (95% CI) for variant alleles=1.22 (0.91-1.61)]. However, mutated ABP1 alleles were present with higher frequency among the 58 patients that required immunosuppressive drugs [OR (95 % CI) for carriers of mutated alleles 2.41 (1.21-4.83; P=0.006)], with a significant gene-dose effect (P=0.0038). In agreement with the predominant role of ABP1 versus HNMT on local histamine metabolism in human bowel, the frequencies for carriers of HNMT genotypes or mutated alleles were similar among patients, regardless clinical evolution, and control individuals. CONCLUSION: The His645Asp polymorphism of the histamine metabolising enzyme ABP1 is related to severity of ulcerative colitis.

Adult↗
PubMed2006

Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals.

Cytochrome P450 (CYP) superfamily members CYP2C8 and CYP2C9 are polymorphically expressed enzymes that are involved in the metabolic inactivation of several drugs, including, among others, antiepileptics, NSAIDs, oral hypoglycemics, and anticoagulants. Many of these drugs have a narrow therapeutic index, and growing evidence indicates a prominent role of CYP2C8 and CYP2C9 polymorphisms in the therapeutic efficacy and in the development of adverse effects among patients treated with drugs that are CYP2C8 or CYP2C9 substrates. In this review, we summarize present knowledge on human variability in the frequency of variant CYP2C8 and CYP2C9 alleles. Besides an expected interethnic variability in allele frequencies, a large intraethnic variability exists. Among Asian subjects, for example, statistically significant differences (p < 0.0001) in CYP2C9*3 allele frequencies between Chinese and Japanese individuals have been reported. In addition, individuals from East Asia present different allele frequencies for CYP2C9*2 and CYP2C9*3 compared with South Asian subjects (p < 0.0001). Among Caucasian Europeans, statistically significant differences for the frequency of CYP2C8*3, CYP2C9*2, and CYP2C9*3 exist (p < 0.0001). This indicates that Asian individuals or Caucasian European individuals cannot be considered as homogeneous groups regarding CYP2C8 or CYP2C9 allele frequencies. Caucasian American subjects also show a large variability in allele frequencies, which is likely to be related to ethnic ancestry. A higher frequency of variant CYP2C8 and CYP2C9 alleles is expected among Caucasian Americans with South European ancestry than in individuals with North European ancestry. The findings summarized in this review suggest that among individuals with Asian or European ancestry, intraethnic differences in the risk of developing adverse effects with drugs that are CYP2C8 or CYP2C9 substrates are to be expected. In addition, the observed intraethnic variability reinforces the need for proper selection of control subjects and points against the use of surrogate control groups for studies involving association of CYP2C8 or CYP2C9 alleles with adverse drug reactions or spontaneous diseases.

Aryl Hydrocarbon Hydroxylases↗
PubMed2006

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.

Adolescent↗
PubMed2006

Mannan-binding lectin pathway deficiencies and invasive fungal infections following allogeneic stem cell transplantation.

OBJECTIVE: The Mannan-binding lectin (MBL) pathway involves recognition of fungal surfaces by MBL and cleavage of C2 and C4 by MBL-associated serine protease (namely, MASP-2). Recent data show that MBL pathway deficiency might result not only from polymorphisms of the MBL2 gene but also of MASP2. The aim of the study was to assess whether polymorphisms of these genes are associated with invasive fungal infections (IFIs) following allogeneic stem cell transplantation (allo-SCT). METHODS: The promoter and the exon 1 of MBL2 and the exon 3 of MASP2 were sequenced in 106 donor-recipient pairs from HLA-identical sibling allo-SCTs performed in a single institution. RESULTS: Ten percent of the donors and 11% of the recipients carried the MBL-low (O/O, LXA/O) genotypes; 7% of the donors and 3% of the recipients were heterozygous for the MASP2 Asp105Gly variant. Factors associated with a higher probability of IFIs were donor's MBL-low genotype (38% vs 12%, p = 0.01), recipient's MASP2 variant (67% vs 14%, p = 0.01), and acute graft-versus-host disease (GVHD) grades II to IV (27% vs 11%, p = 0.04); in the multivariate analysis MBL-low genotype (relative risk [RR] 7.3, p = 0.003), MASP2 variant (RR 6.4, p = 0.002), and acute GVHD II to IV (RR 3.8, p = 0.02) retained independent prognostic value. CONCLUSION: These results show for the first time that polymorphisms responsible for not only MBL but also MASP-2 deficiency are independent predictive factors for IFI after allo-SCT.

Acute Disease↗
PubMed2006

Fathers and gender traditionalism: perception of inequality and life roles.

Men's discourse about the paternal role is changing significantly. Despite the fact that men still perceive themselves as being responsible for the family's economical protection and the children's discipline, they face increasing demands for more involvement in childcare. From this perspective, this work analyzes the traditional view of gender roles and the perception of inequality in a sample of 95 employed fathers, as well as the various levels of satisfaction with other life roles and their relevance as a function of some gender and sociodemographic variables. The results show that men do not maintain a very traditional gender ideology with regard to role distribution and they still consider the paternal role and feelings as the most important thing in their lives. However, the couple relationship gives them the most satisfaction. Level of traditionalism and age were the two significant predicting variables of perception of inequality of men and women.

Adult↗
PubMed2006

Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition.

Metabolizing enzymes, which often display genetic polymorphisms, are involved in the activation of compounds present in tobacco smoke that may be relevant to gastric carcinogenesis. We report the results of a study looking at the association between risk of gastric adenocarcinoma and polymorphisms in genes CYP1A1, CYP1A2, EPHX1, and GSTT1. A nested case-control study was carried out within the European Prospective Investigation into Cancer and Nutrition, developed in 10 European countries. The study includes 243 newly diagnosed cases of histologically confirmed gastric adenocarcinoma and 946 controls matched by center, age, sex, and date of blood collection. Genotypes were determined in nuclear DNA from WBCs. We found an increased risk of gastric cancer for homozygotes for C (histidine) variant in Y113H of EPHX1 (odds ratio, 1.91; 95% confidence interval, 1.19-3.07) compared with subjects with TC/TT. There was also a significant increased risk for smokers carrying at least one variant allele A in Ex7+129C>A (m4) of CYP1A1 and never smokers with null GSTT1 and allele A in the locus -3859G>A of CYP1A2. Most of these genes are involved in the activation and detoxification of polycyclic aromatic hydrocarbons, suggesting a potential role of these compounds in gastric carcinogenesis.

Adenocarcinoma↗
PubMed2006

Effect of VIP on TLR2 and TLR4 expression in lymph node immune cells during TNBS-induced colitis.

Toll-like receptors (TLRs) are a family of pattern recognition receptors (PRRs), which recognize numerous molecules collectively named pathogen-associated molecular patterns, with an essential role in inflammatory conditions and connecting innate and acquired immune responses. Moreover, a new function of TLRs in the intestinal mucosa has been described. Under homeostatic conditions, TLRs act to protect the intestinal epithelium; but when homeostasis is disrupted, TLRs appear deregulated. Disruption of intestinal homeostasis occurs in disorders, such as Crohn's disease (CD). Trinitrobenzene sulfonic acid (TNBS)-induced colitis is a murine model of human CD and vasoactive intestinal polypeptide (VIP) exerts a beneficial effect, by decreasing both inflammatory and autoimmune components of the disease. Recently, we have demonstrated the constitutive expression of TLR2 and TLR4 at mRNA and protein levels in colon extracts and their upregulation in TNBS-treated mice as well as the effect of VIP treatment, approaching control levels. However, the systemic effect is little known. The present results demonstrate a beneficial role of VIP, restoring homeostatic conditions through the regulation of both lymphoid cell traffic and TLR2/4 expression on macrophages (MØ), dendritic cells (DCs), and CD4 and CD8 T lymphocytes.

Animals↗
PubMed2006

PAC1 receptor: emerging target for septic shock therapy.

Septic shock is a systemic response to severe bacterial infections, generally caused by Gram-negative bacterial endotoxins, with multiple manifestations such as hypotension, tissue injury, disseminated intravascular coagulation, and multi-organ failure. All these effects, are induced by the generation of pro-inflammatory and vasodilator mediators, cell adhesion molecules, coagulation factors, and acute-phase proteins. Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two immunopeptides with anti-inflammatory properties exerted through type 1 and 2 VIP receptors (VPAC1 and VPAC2, respectively), and PACAP receptor (PAC1). The present results recapitulate the protective role of PAC1 in an experimental model of lethal endotoxemia using a knockout for the PAC1 receptor. Our results demonstrate that VIP and PACAP decrease lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) production, neutrophil infiltration and intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and fibrinogen expression through PAC1 receptor, providing an advantage to design more specific drugs complementing standard intensive care therapy in septic shock.

Animals↗
PubMed2006

Acquired resistance to the anticancer drug paclitaxel is associated with induction of cytochrome P450 2C8.

INTRODUCTION: We have previously shown that human colorectal cancer tissue is able to inactivate the anticancer drug paclitaxel through cytochrome P450 (CYP)2C8 and CYP3A4 metabolisms. The aim of this study was to evaluate whether changes in the expression levels of genes coding for such enzymes are related to anticancer drug resistance after long-term exposure to the drug. METHODS: Human colorectal cancer cells (Caco-2) that are sensitive to paclitaxel were exposed to increasing concentrations of the drug from 0-250 nM during one year, in order to select paclitaxel-resistant cells. Subsequently, we compared the sensitivity to paclitaxel and the extent of expression of the CYP2C8, CYP3A4 and CYP3A5 genes in original and resistant cells. RESULTS: Resistant cancer cells displayed a 246-fold increased lethal dose (LD)50 to paclitaxel (p < 0.004) as compared with original cancer cells. A 4.4-fold (p = 0.005) enhancement of CYP2C8 expression and a 5.6-fold (p = 0.001) increase of multidrug resistance (MDR)1 expression was observed in resistant cells exposed to paclitaxel. When paclitaxel was removed from the culture medium, CYP2C8, but not MDR1 expression, reverted to basal levels and the resistance to paclitaxel decreased 3.2-fold (p = 0.005). No major changes in the expression levels of CYP3A4 and CYP3A5 were observed. CONCLUSIONS: Caco-2 cells are capable of increasing the expression levels of CYP2C8 as a response to long-term exposure to paclitaxel. This study provides evidence for a mechanism of acquired resistance to anticancer therapy based on the induction of anticancer-metabolizing enzymes.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Glutathione S-transferases mu 1, theta 1, pi 1, alpha 1 and mu 3 genetic polymorphisms and the risk of colorectal and gastric cancers in humans.

INTRODUCTION: Glutathione S-transferases (GSTs) are considered to be cancer susceptibility genes as they play a role in the detoxification of carcinogenic species. This study aimed to elucidate the influence of several GST polymorphisms on colorectal and gastric cancer risk. PATIENTS AND METHODS: GST mu1 (GSTM1), theta1 (GSTT1), pi1 (GSTP1), alpha1 (GSTA1) and mu3 (GSTM3) genotypes were determined in 144 colorectal cancer patients, 98 gastric cancer patients and 329 healthy control individuals. RESULTS: Colorectal cancer: the risk is greater for carriers of the GSTM1 null genotype (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.25-2.91), for carriers of the GSTT1 null genotype (OR = 3.62, 95% CI = 2.34-5.62), and for simultaneous carriers of both GSTM1 and GSTT1 null genotypes (OR = 4.98, 95% CI = 2.77-9.00). Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.31, 95% CI = 0.09-0.88). Among carriers of the GSTP1 Ile/Ile genotype, smoking increases the risk compared with nonsmoking (OR = 2.35, 95% CI = 1.11-4.99). Gastric cancer: the risk is greater for carriers of the GSTT1 null genotype (OR = 2.58, 95% CI = 1.53-4.36) and for simultaneous carriers of both GSTM1 and GSTT1 null genotypes (OR = 3.32, 95% CI = 1.62-6.77). Carriers of the GSTP1 104 Val/Val genotype are at a lower risk (OR = 0.20, 95% CI = 0.02-0.86). DISCUSSION: The GSTT1 null genotype, particularly if it is associated with the GSTM1 null genotype, greatly increases the risk for colorectal and gastric cancers. The GSTP1 104 Val/Val genotype may protect from both malignant tumors. CONCLUSION: This study indicates that GST polymorphisms, in particular the GSTM1/GSTT1 double-null haplotype, can be considered low-penetrance genes for gastrointestinal cancer.

Aged↗
PubMed2006

Effect of NOD2/CARD15 variants in T-cell depleted allogeneic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Three single nucleotide polymorphisms (SNP) in the NOD2/CARD15 gene have been associated with the incidence and the severity of acute graft-versus-host disease (GVHD) following allogeneic stem cell transplantation (SCT). We hypothesized that the clinical effect of SNP in NOD2/CARD15 might be different in patients submitted to T-cell-depleted allogeneic SCT, in which donor T cells, the main effectors of GVHD, are eliminated. DESIGN AND METHODS: SNP 8, 12 and 13 in NOD2/CARD15 were studied using a Taqman protocol in 85 patients undergoing HLA-identical, T-cell-depleted SCT and in 71 of their sibling donors. RESULTS: NOD2/CARD15 variants were present in nine (11%) patients and six (8%) donors. The incidences of acute GVHD and chronic GVHD were not associated with either the donors' or recipients' NOD2/CARD15 variants. In contrast, these genetic variants were associated with a lower disease-free survival (17% vs. 48%, p=0.03). Death due to pulmonary infection was more frequent in the group of patients with NOD2/CARD15 variants. In the multivariate analysis, only NOD2/CARD15 variants (RR 2.3, p=0.04) and older age (RR 2.2; p=0.04) were independent prognostic factors for disease-free survival. INTERPRETATION AND CONCLUSIONS: NOD2/CARD15 variants have a deleterious effect on clinical outcome in T-cell-depleted allogeneic SCT, which is independent of GVHD. These results supports the hypothesis that the detrimental effect of NOD2/CARD15 variants in such a transplant setting might be produced by an alteration of the innate immune system more than by activation of the adaptive immune system.

Adult↗
PubMed2005

Glutathione S-transferase M1 and T1 genetic polymorphisms are not related to the risk of hepatocellular carcinoma: a study in the Spanish population.

Glutathione S-transferases constitute a superfamily of enzymes that catalyse the inactivating conjugation of endogenous and environmental substrates involved in the pathogenesis of hepatocellular carcinoma (HCC) and glutathione. Genes encoding either glutathione S-transferase Mu-1 or Theta-1 (GSTM1 and GSTT1, respectively) isoforms are polymorphic. Homozygotes for the mutated inactive alleles of each gene are devoid of any specific enzymatic activity (null genotypes). Our aim was to investigate whether individuals with null GST genotypes have a higher risk of developing HCC. A total of 184 Caucasian Spanish patients with a diagnosis of HCC and 329 healthy controls of the same ethnic origin were included. Polymorphisms in GSTM1 and GSTT1 genes were identified through multiplex polymerase chain reactions, and the dihydrofolate reductase (DHFR) gene was used as internal control. No differences were found between the frequencies of GSTM1 (47.8% versus 45.3%) and GSTT1 (28.8% versus 23.1%) null genotypes in cases and controls, respectively, nor in the proportion of carriers of two, one or no active genotypes. Gender, age at diagnosis, tobacco use, chronic infection with hepatitis B or C virus and alcohol abuse did not influence these results. In conclusion, polymorphisms in GSTM1 and GSTT1 genes are not related to the incidence of HCC in a high-risk Spanish population.

Aged↗