Редактирование: ERCC2 (раздел)

==Publications==

{{medline-entry
|title=The genetic component of human longevity: New insights from the analysis of pathway-based SNP-SNP interactions.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29577582
|abstract=In human longevity studies, single nucleotide polymorphism (SNP) analysis identified a large number of genetic variants with small effects, yet not easily replicable in different populations. New insights may come from the combined analysis of different SNPs, especially when grouped by metabolic pathway. We applied this approach to study the joint effect on longevity of SNPs belonging to three candidate pathways, the insulin/insulin-like growth factor signalling (IIS), DNA repair and pro/antioxidant. We analysed data from 1,058 tagging SNPs in 140 genes, collected in 1825 subjects (1,089 unrelated nonagenarians from the Danish 1905 Birth Cohort Study and 736 Danish controls aged 46-55 years) for evaluating synergic interactions by SNPsyn. Synergies were further tested by the multidimensional reduction (MDR) approach, both intra- and interpathways. The best combinations (FDR<0.0001) resulted those encompassing [[IGF1R]]-rs12437963 and [[PTPN1]]-rs6067484, [[TP53]]-rs2078486 and [[ERCC2]]-rs50871, [[TXNRD1]]-rs17202060 and [[TP53]]-rs2078486, the latter two supporting a central role of [[TP53]] in mediating the concerted activation of the DNA repair and pro-antioxidant pathways in human longevity. Results were consistently replicated with both approaches, as well as a significant effect on longevity was found for the [[GHSR]] gene, which also interacts with partners belonging to both IIS and DNA repair pathways (PAPPA, [[PTPN1]], [[PARK7]], MRE11A). The combination [[GHSR]]-MREA11, positively associated with longevity by MDR, was further found influencing longitudinal survival in nonagenarian females (p = .026). Results here presented highlight the validity of SNP-SNP interactions analyses for investigating the genetics of human longevity, confirming previously identified markers but also pointing to novel genes as central nodes of additional networks involved in human longevity.
|mesh-terms=* Aging
* Female
* Humans
* Longevity
* Male
* Polymorphism, Single Nucleotide
* Survival Analysis
|keywords=* 
SNP

* aging
* epistasis
* genetic component of human longevity
* pathway-based analysis
* synergic interaction
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946073
}}
{{medline-entry
|title=Inter-individual variation in nucleotide excision repair in young adults: effects of age, adiposity, micronutrient supplementation and genotype.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18838045
|abstract=Nucleotide excision repair (NER) is responsible for repairing bulky helix-distorting DNA lesions and is essential for the maintenance of genomic integrity. Severe hereditary impairment of NER leads to cancers such as those in xeroderma pigmentosum, and more moderate reductions in NER capacity have been associated with an increased cancer risk. Diet is a proven modifier of cancer risk but few studies have investigated the potential relationships between diet and NER. In the present study, the plasmid-based host cell reactivation assay was used to measure the NER capacity in peripheral blood mononuclear cells from fifty-seven volunteers aged 18-30 years before and after 6 weeks of supplementation with micronutrients (selenium and vitamins A, C and E). As a control, nine individuals remained unsupplemented over the same period. Volunteers were genotyped for the following polymorphisms in NER genes: [[ERCC5]] Asp1104His (rs17655); [[XPC]] Lys939Gln (rs2228001); [[ERCC2]] Lys751Gnl (rs13181); [[XPC]] PAT (an 83 bp poly A/T insertion-deletion polymorphism in the [[XPC]] gene). NER capacity varied 11-fold between individuals and was inversely associated with age and endogenous DNA strand breaks. For the first time, we observed an inverse association between adiposity and NER. No single polymorphism was associated with the NER capacity, although significant gene-gene interactions were observed between [[XPC]] Lys939Gln and [[ERCC5]] Asp1104His and [[XPC]] Lys939Gln and [[ERCC2]] Lys751Gnl. While there was no detectable effect of micronutrient supplementation on NER capacity, there was evidence that the effect of fruit intake on the NER capacity may be modulated by the [[ERCC2]] Lys751Gnl single nucleotide polymorphism.
|mesh-terms=* Adiposity
* Adolescent
* Adult
* Aging
* Body Mass Index
* DNA Repair
* Diet
* Dietary Supplements
* Female
* Genotype
* Humans
* Male
* Micronutrients
* Polymorphism, Genetic
* Young Adult

|full-text-url=https://sci-hub.do/10.1017/S0007114508076265
}}