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Individually tailored screening of susceptibility to sarcopenia using p53 codon 72 polymorphism, phenotypes, and conventional risk factors.

ABSTRACT: BACKGROUND AND AIM:p53 activity plays a role in muscle homeostasis and skeletal muscle differentiation; all pathways that lead to sarcopenia are related to p53 activities. We investigate the allelic frequency of the TP53 codon 72 in exon 4 polymorphism in the Italian female population and the association with appendicular skeletal muscle mass index in normal weight (NW), normal weight obese (NWO), and preobese-obese (Preob-Ob) subjects. METHODS:We evaluated anthropometry, body composition, and p53 polymorphism in 140 women distinguished in NW, NWO, and Preob-Ob. RESULTS:*Arg/*Arg genotype increases sarcopenia risk up to 20% (*Arg/*Arg genotype OR = 1.20; 95% CI = 0.48-2.9; *proallele carriers OR = 0.83; 95% CI = 0.83-2.06). The risk of being sarcopenic for *Arg/*Arg genotype in NWO and Preob-Ob is 31% higher than NW carriers of *proallele (RR = 0,31, 95% CI = 0,15-0,66, P = 0,0079). We developed a model able to predict sarcopenia risk based on age, body fat, and p53 polymorphism. CONCLUSION:Our study evidences that genotyping TP53 polymorphism could be a useful new genetic approach, in association with body composition evaluations, to assess sarcopenia risk.

SUBMITTER: Di Renzo L

PROVIDER: S-EPMC4211310 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Individually tailored screening of susceptibility to sarcopenia using p53 codon 72 polymorphism, phenotypes, and conventional risk factors.

Di Renzo Laura L Gratteri Santo S Sarlo Francesca F Cabibbo Andrea A Colica Carmen C De Lorenzo Antonino A

Disease markers 20141013

<h4>Background and aim</h4>p53 activity plays a role in muscle homeostasis and skeletal muscle differentiation; all pathways that lead to sarcopenia are related to p53 activities. We investigate the allelic frequency of the TP53 codon 72 in exon 4 polymorphism in the Italian female population and the association with appendicular skeletal muscle mass index in normal weight (NW), normal weight obese (NWO), and preobese-obese (Preob-Ob) subjects.<h4>Methods</h4>We evaluated anthropometry, body com ...[more]

PMID: 25371596

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Project description:IntroductionThe absence of mutation or promoter hypermethylation in the BRCA2 gene in the majority of breast cancer cases has indicated alternative ways of its involvement, deregulated expression being one possibility. We show how a polymorphism in the 5' untranslated region (UTR) of BRCA2 can serve as one such factor. Based on the hypothesis that variants of genes involved in the same pathway can influence the risk provided for breast cancer, the status of p53 codon 72 polymorphism was also investigated and a possible interaction between the polymorphisms was examined.MethodsThe luciferase reporter assay followed by RNA secondary structure analysis was used for the functional characterization of -26 5' UTR G>A polymorphism in BRCA2. The genotype and the allele frequency for the polymorphisms were determined and relative risk adjusted for age was calculated in a case-control study of 576 individuals (243 patients and 333 controls) from north India.Results-26 G>A polymorphism in the 5' UTR of BRCA2 was found to be functional whereby the A allele increased the reporter gene expression by twice that of the G allele in MCF-7 (P = 0.003) and HeLa (P = 0.013) cells. RNA secondary structure analysis by two different programs predicted the A allele to alter the stability of a loop in the vicinity of the translation start site. Its direct implication in breast cancer became evident by a case-control study in which the heterozygous genotype was found to be protective in nature (P heterozygote advantage model = 0.0005, odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.4 to 0.8), which was further supported by trends observed in a genomic instability study. The p53 codon 72 Arg homozygous genotype was found to be over-represented in patients (P = 0.0005, OR = 2.3, 95% CI = 1.4 to 3.6). The interaction study indicated an increased protection under simultaneous presence of protector genotypes of both the polymorphic loci (P = 0.0001, OR = 0.2, 95% CI = 0.1 to 0.4).ConclusionOur study shows that -26 5' UTR polymorphism in BRCA2 can modulate the fine-tuned regulation of the multifunctional gene BRCA2 and renders risk or protection according to the genotype status in the sporadic form of breast cancer, which is further influenced by the germline genetic backgrounds of codon 72 polymorphism of p53.

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Individually tailored screening of susceptibility to sarcopenia using p53 codon 72 polymorphism, phenotypes, and conventional risk factors.

Publications

Individually tailored screening of susceptibility to sarcopenia using p53 codon 72 polymorphism, phenotypes, and conventional risk factors.

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