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Genetic polymorphisms for histamine-metabolizing enzymes are responsible for interindividual variation in histamine metabolism and are associated with diverse diseases. Initial reports on polymorphisms of histamine-related genes including those coding for the enzymes histidine decarboxylase (HDC), diamine oxidase (ABP1) and histamine -methyltransferase (HNMT), as well as histamine receptor genes, often have pointed to polymorphisms that occur with extremely low frequencies or that could not be verified by later studies. In contrast, common and functionally significant polymorphisms recently described have been omitted in many association studies. In this review we analyze allele frequencies, functional and clinical impact and interethnic variability on histamine-related polymorphisms. The most relevant nonsynonymous polymorphisms for the gene are rs17740607 Met31Thr, rs16963486 Leu553Phe and rs2073440 Asp644Glu. For the most relevant polymorphisms are rs10156191 Thr16Met, rs1049742 Ser332Phe, and particularly because of its functional effect, rs1049793 His645Asp. In addition the polymorphisms rs45558339 Ile479Met and rs35070995 His659Asn are relevant to Asian and African subjects, respectively. For the only nonsynonymous polymorphism present with a relevant frequency is rs1801105 Thr105Ile. For the polymorphism rs7651620 Glu270Gly is relevant to African subjects only. The rs2067474 polymorphism, located in an enhancer element of the gene promoter, is common in all populations. No common nonsynonymous SNPs were observed in the gene and two SNPs were observed with a significant frequency in the gene: rs11665084 Ala138Val and rs11662595 His206Arg. This review summarizes relevant polymorphisms, discusses controversial findings on association of histamine-related polymorphisms and allergies and other diseases, and identifies topics requiring further investigation.

We study the spectrum of periodic Jacobi matrices. We concentrate on the case of slowly oscillating diagonal terms and study the behaviour of the zeros of the associated orthogonal polynomials in the spectral gap. We find precise estimates for the distance from single eigenvalues of truncated matrices in the spectral gap to the diagonal entries of the matrix. We include a brief numerical example to show the exactness of our estimates.

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. 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 , and genes in original and resistant cells. Resistant cancer cells displayed a 246-fold increased lethal dose (LD) to paclitaxel (p  <  0.004) as compared with original cancer cells. A 4.4-fold (p  =  0.005) enhancement of 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, but not 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 and were observed. Caco-2 cells are capable of increasing the expression levels of 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.

Introduction: Glutathione S-transferases ππ1, αα1 and µµ3 are members of an enzymatic superfamily involved in the conjugation and detoxification of carcinogens. Polymorphisms affecting the genes encoding these enzymes may modify their ability to neutralize carcinogens. Our aim was to investigate whether these polymorphisms affect the risk of developing hepatocellular carcinoma in humans. Methods: A total of 184 white Spanish patients diagnosed with hepatocellular carcinoma and 248 healthy control subjects from the same ethnic origin were included. GSTA1*B promoter allele, GSTM3*B 3-bp-deleted allele and GSTP1 Ile105Val SNP were identified. Results: No differences were found between the distribution of the studied polymorphisms, or in the allele frequencies for variant alleles in patients and controls: 0.411 and 0.371 for GSTA1, 0.116 and 0.131 for GSTM3, and 0.285 and 0.309 for GSTP1, respectively. Among patients the GSTP1 mutated allele was more frequent in those drinking more than 50 g ethanol/day (odds ratio: 2.00; 95% confidence intervals: 1.06--3.78). Age at diagnosis, gender, tobacco use and hepatitis B and C viral status did not influence these results. Conclusion: We conclude that the studied polymorphisms affecting GSTP1, GSTA1 and GSTM3 genes are probably not related to the risk of developing hepatocellular carcinoma in the studied population.

Glutathione -transferases π1, αα1 and µµ3 are members of an enzymatic superfamily involved in the conjugation and detoxification of carcinogens. Polymorphisms affecting the genes encoding these enzymes may modify their ability to neutralize carcinogens. Our aim was to investigate whether these polymorphisms affect the risk of developing hepatocellular carcinoma in humans. A total of 184 white Spanish patients diagnosed with hepatocellular carcinoma and 248 healthy control subjects from the same ethnic origin were included. promoter allele, 3-bp-deleted allele and Ile105Val SNP were identified. No differences were found between the distribution of the studied polymorphisms, or in the allele frequencies for variant alleles in patients and controls: 0.411 and 0.371 for , 0.116 and 0.131 for , and 0.285 and 0.309 for , respectively. Among patients the mutated allele was more frequent in those drinking more than 50  g ethanol/day (odds ratio: 2.00; 95% confidence intervals: 1.06-–3.78). Age at diagnosis, gender, tobacco use and hepatitis B and C viral status did not influence these results. We conclude that the studied polymorphisms affecting and genes are probably not related to the risk of developing hepatocellular carcinoma in the studied population.

Introduction: Glutathione S-transferases pi pi 1, alpha alpha 1 and mu mu 3 are members of an enzymatic superfamily involved in the conjugation and detoxification of carcinogens. Polymorphisms affecting the genes encoding these enzymes may modify their ability to neutralize carcinogens. Our aim was to investigate whether these polymorphisms affect the risk of developing hepatocellular carcinoma in humans. Methods: A total of 184 white Spanish patients diagnosed with hepatocellular carcinoma and 248 healthy control subjects from the same ethnic origin were included. GSTA1*B promoter allele, GSTM3*B 3-bp-deleted allele and GSTP1 Ile105Val SNP were identified. Results: No differences were found between the distribution of the studied polymorphisms, or in the allele frequencies for variant alleles in patients and controls: 0.411 and 0.371 for GSTA1, 0.116 and 0.131 for GSTM3, and 0.285 and 0.309 for GSTP1, respectively. Among patients the GSTP1 mutated allele was more frequent in those drinking more than 50g ethanol/day (odds ratio: 2.00; 95% confidence intervals: 1.06--3.78). Age at diagnosis, gender, tobacco use and hepatitis B and C viral status did not influence these results. Conclusion: We conclude that the studied polymorphisms affecting GSTP1, GSTA1 and GSTM3 genes are probably not related to the risk of developing hepatocellular carcinoma in the studied population.