Home About us Contact
|
Home About us Contact | ||
|
|
||
Deficiency Alleles (deficiency + allele)
Selected AbstractsThiopurine S -methyltransferase (TPMT) genetic polymorphisms in Mexican newbornsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2009A. González-del Angel MD Abstract Background:, Thiopurine S -methyltransferase (TPMT) is involved in the toxicity and therapeutic efficacy of thiopurine drugs, and its gene exhibits genetic polymorphisms that differ across diverse populations. Four TPMT polymorphisms (TPMT*2, *3A, *3B and *3C) account for 80,95% of alleles that cause reduced enzyme activity. To date, only a single study in the Mexican population involving 108 individuals has been performed, but the regional and ethnic origin of this population was not described. Accordingly, information about the TPMT polymorphism in the Mexican population is limited. Objective:, To determine the TPMT allele and genotype frequencies in a sample of newborns from Mexico City. Methods:, Three hundred and sixty DNA samples from unrelated, anonymous individuals were obtained from dried blood spots collected on filter paper as part of the Newborn Screening National Program. Allele-specific polymerase chain reaction for the TPMT*2 allele and PCR restriction fragment length polymorphism for TPMT*3A, TPMT*3B, TPMT*3C alleles were used to determine the respective allelic and genotypic frequencies. Results and Discussion:, Of 720 TPMT alleles analysed, 49 (6·81%) were deficiency alleles. The most common deficiency allele was TPMT*3A (5·69%), followed by TPMT*3C (0·56%), TPMT*3B (0·28%) and TPMT*2 (0·28%). Fourty-five newborns were heterozygous for one mutant allele (12·5%) and two showed a genotype with two deficiency alleles (0·56%). Despite its unique ethnic composition, our Mexican population exhibited variant allele frequencies that were similar to some Caucasian populations. Conclusion:, Our data suggest that approximately 1 in 180 persons born in Mexico City might have low or undetectable TPMT enzyme activity, a frequency that, overall, is somewhat higher than that reported for Caucasian populations generally (1 in 300). [source] Analysis of two common ,1 -antitrypsin deficiency alleles (PI*Z and PI*S) in subjects with periodontitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 12 2002D. A. Scott Abstract Background: ,,1 -Antitrypsin deficiency is a genetically determined condition resulting in predisposition to certain inflammatory diseases due to a protease: antiprotease imbalance that is exacerbated by tobacco smoking. Limited evidence suggests that there may be a significant enrichment of mild ,1 -antitrypsin deficiency phenotypes in subjects with chronic inflammatory periodontal disease. Objective: To examine the prevalence of two common ,1 -antitrypsin deficiency alleles (PI*Z and PI*S) in a UK population of subjects with periodontitis. Subjects and methods: The prevalence of PI*M, PI*S and PI*Z allele combinations was determined in 31 subjects with periodontitis and compared with 31 healthy control subjects matched for smoking status, ethnicity, age and gender. ,1 -Antitrypsin genotyping was performed by multiplex real-time fluorescence polymerase chain reaction (PCR) using DNA extracted from whole blood. Results: There was no difference in the proportion of any ,1 -antitrypsin genotype found in the diseased and control populations. Conclusions: We did not find evidence to support an association between mutant PI* alleles and periodontitis in a small, controlled study. Larger studies will be required to clarify the relationship between ,1 -antitrypsin genotype and susceptibility to inflammatory periodontal disease. [source] Thiopurine S -methyltransferase (TPMT) genetic polymorphisms in Mexican newbornsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 6 2009A. González-del Angel MD Abstract Background:, Thiopurine S -methyltransferase (TPMT) is involved in the toxicity and therapeutic efficacy of thiopurine drugs, and its gene exhibits genetic polymorphisms that differ across diverse populations. Four TPMT polymorphisms (TPMT*2, *3A, *3B and *3C) account for 80,95% of alleles that cause reduced enzyme activity. To date, only a single study in the Mexican population involving 108 individuals has been performed, but the regional and ethnic origin of this population was not described. Accordingly, information about the TPMT polymorphism in the Mexican population is limited. Objective:, To determine the TPMT allele and genotype frequencies in a sample of newborns from Mexico City. Methods:, Three hundred and sixty DNA samples from unrelated, anonymous individuals were obtained from dried blood spots collected on filter paper as part of the Newborn Screening National Program. Allele-specific polymerase chain reaction for the TPMT*2 allele and PCR restriction fragment length polymorphism for TPMT*3A, TPMT*3B, TPMT*3C alleles were used to determine the respective allelic and genotypic frequencies. Results and Discussion:, Of 720 TPMT alleles analysed, 49 (6·81%) were deficiency alleles. The most common deficiency allele was TPMT*3A (5·69%), followed by TPMT*3C (0·56%), TPMT*3B (0·28%) and TPMT*2 (0·28%). Fourty-five newborns were heterozygous for one mutant allele (12·5%) and two showed a genotype with two deficiency alleles (0·56%). Despite its unique ethnic composition, our Mexican population exhibited variant allele frequencies that were similar to some Caucasian populations. Conclusion:, Our data suggest that approximately 1 in 180 persons born in Mexico City might have low or undetectable TPMT enzyme activity, a frequency that, overall, is somewhat higher than that reported for Caucasian populations generally (1 in 300). [source] The low frequency of defective TPMT alleles in Turkish population: A study on pediatric patients with acute lymphoblastic leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2007Tugba Boyunegmez Tumer 6-Mercaptopurine (6MP) is an essential anticancer drug used in the treatment of childhood acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe toxicity or efficacy of 6MP. Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C, are responsible over the 80% of low or undetectable enzyme activity. The frequencies of these variants were investigated among 106 children with ALL in Turkish population. TPMT*3A and TPMT*3C were the only deficiency alleles detected in Turkish population with an allele frequency of 0.9% for both. While *3C allele frequency in Turkish population was found to be very similar to Asian and other Caucasian populations, *3A allele frequency was significantly (P < 0.05) lower. So far, studies showed that the genetic polymorphisms of other drug metabolizing enzymes like CYP2E1, CYP1A1, GSTM1/ T1 in Turkish population were similar to Caucasian populations. However, we found that the distribution of TPMT polymorphisms in Turkish population was significantly lower than those in other Caucasians like British, French, and Italian whereas the distributions of TPMT variants were found to be very similar to Kazak population which is also Caucasian in ethnic origin. In this study, the clinical histories of the patients in the sample population were also examined, retrospectively. The patients with heterozygous or homozygous mutant genotypes had developed severe neutropenia and infection during 6MP therapy. The study provides the first data on the frequency of common TPMT variants in the Turkish population, based on analysis of pediatric patients with ALL. Am. J. Hematol. 82:906,910, 2007. © 2007 Wiley-Liss, Inc. [source] Alpha 1 antitrypsin deficiency alleles are associated with joint dislocation and scoliosis in Williams syndrome,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2010Colleen A. Morris Abstract Elastin haploinsufficiency is responsible for a significant portion of the Williams syndrome (WS) phenotype including hoarse voice, supravalvar aortic stenosis (SVAS), hernias, diverticuli of bowel and bladder, soft skin, and joint abnormalities. All of the connective tissue signs and symptoms are variable in the WS population, but few factors other than age and gender are known to influence the phenotype. We examined a cohort of 205 individuals with WS for mutations in SERPINA1, the gene that encodes alpha-1-antitrypsin (AAT), the inhibitor of elastase. Individuals with classic WS deletions and SERPINA1 genotypes PiMS or PiMZ were more likely than those with a SERPINA1 PiMM genotype to have joint dislocation or scoliosis. However, carrier status for AAT deficiency was not correlated with presence of inguinal hernia or with presence or severity of SVAS. These findings suggest that genes important in elastin metabolism are candidates for variability in the connective tissue abnormalities in WS. © 2010 Wiley-Liss, Inc. [source] | ||||||||||