Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a Spanish family with muscle glycogen phosphorylase (PYGM) deficiency (McArdle's disease) harbouring a novel compound genotype (A659D/L586P). Four individuals who had the same genotype for PYGM, showed a wide variability in the presentation of the clinical phenotype, including one patient with a restrictive respiratory pattern, which is unusual in McArdle's disease. Moreover, these patients were studied for the insertion/deletion (I/D) trait in the angiotensin converting enzyme (ACE) which has been suggested to be a strong modulator of severity in McArdle's disease. Our results indicate no association of the I/D ACE trait in this family, suggesting that other factors would be more relevant in determining the severity of the clinical presentation.
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PMID:Variable presentation of the clinical phenotype of McArdle's disease in a kindred harbouring a novel compound genotype in the muscle glycogen phosphorylase gene. 1615 88

The phenotypic manifestation of McArdle disease varies considerably from one individual to the next. The purpose of this study was to assess the possible association between the clinical severity of the disease, and each of the genotypes PYGM (R50X), ACE (I/D), AMPD1 (Q12X), PPARGC1A (G482S) and ACTN3 (R577X). We also assessed links between clinical disease severity and other potential phenotype modulators such as age or gender. McArdle disease was diagnosed in 99 patients of Spanish origin (60 male, 39 female; age range 8-81 years) by identifying the two mutant alleles of the PYGM gene. Disease severity was assessed using the grading scheme previously reported by Martinuzzi et al. [A. Martinuzzi, E. Sartori, M. Fanin, et al., Phenotype modulators in myophosphorylase deficiency, Ann. Neurol. 53 (2003) 497-502]. Significant correlation was observed (exact two-sided P<0.0001) between the number of D alleles of the ACE gene and the disease severity score. Rank-order correlation coefficients were 0.296 (95% CI: 0.169, 0.423) (Kendall's tau) and 0.345 (95% CI: 0.204, 0.486) (Somer's D). No significant relationships were detected between clinical severity and the remaining genotypes examined. Finally, disease severity was significantly worse in women with the disease. Our findings indicate that both ACE genotype and gender contribute to how McArdle disease manifests in an individual patient. The role of other candidate genes remains to be elucidated.
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PMID:Genotype modulators of clinical severity in McArdle disease. 1763 Feb 10

A small number of excellent articles on exercise genomics issues were published in 2012. A new PYGM knock-in mouse model will provide opportunities to investigate the exercise intolerance and very low activity level of people with McArdle disease. New reports on variants in ACTN3 and ACE have increased the level of uncertainty regarding their true role in skeletal muscle metabolism and strength traits. The evidence continues to accumulate on the positive effects of regular physical activity on body mass index or adiposity in individuals at risk of obesity as assessed by their FTO genotype or by the number of risk alleles they carry at multiple obesity-susceptibility loci. The serum levels of triglycerides and the risk of hypertriglyceridemia were shown to be influenced by the interactions between a single nucleotide polymorphism (SNP) in the NOS3 gene and physical activity level. Allelic variation at nine SNPs was shown to account for the heritable component of the changes in submaximal exercise heart rate induced by the HERITAGE Family Study exercise program. SNPs at the RBPMS, YWHAQ, and CREB1 loci were found to be particularly strong predictors of the changes in submaximal exercise heart rate. The 2012 review ends with comments on the importance of relying more on experimental data, the urgency of identifying panels of genomic predictors of the response to regular exercise and particularly of adverse responses, and the exciting opportunities offered by recent advances in our understanding of the global architecture of the human genome as reported by the Encyclopedia of DNA Elements project.
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PMID:Advances in exercise, fitness, and performance genomics in 2012. 2347 Feb 94