A Common Copy Number Variation Polymorphism in the &lt;b&gt;&lt;i&gt;CNTNAP2&lt;/i&gt;&lt;/b&gt; Gene: Sexual Dimorphism in Association with Healthy Aging and Disease

Iakoubov, Leonid; Mossakowska, Małgorzata; Szwed, Małgorzata; Puzianowska-Kuźnicka, Monika

doi:10.1159/000363320

Cited by 11 publications

(11 citation statements)

References 26 publications

(43 reference statements)

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“…Nevertheless, it has been shown recently that individuals from families enriched for persons displaying exceptional survival exhibited a marked delay in the onset of age-related diseases and comorbidities [ 5 ], suggesting a genetic component. Indeed, such genetic factors have been identified [ 6 ]. Diseases and disorders of aging have figured into other measures of healthy aging, but in and of itself, absence of disease is not useful when categorizing healthy aging, since few people escape unscathed with increasing age.…”

Section: Introductionmentioning

confidence: 99%

Quantitative measures of healthy aging and biological age

Kim

Jazwinski

2015

Healthy Aging Res

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Numerous genetic and non-genetic factors contribute to aging. To facilitate the study of these factors, various descriptors of biological aging, including ‘successful aging’ and ‘frailty’, have been put forth as integrative functional measures of aging. A separate but related quantitative approach is the ‘frailty index’, which has been operationalized and frequently used. Various frailty indices have been constructed. Although based on different numbers and types of health variables, frailty indices possess several common properties that make them useful across different studies. We have been using a frailty index termed FI34 based on 34 health variables. Like other frailty indices, FI34 increases non-linearly with advancing age and is a better indicator of biological aging than chronological age. FI34 has a substantial genetic basis. Using FI34, we found elevated levels of resting metabolic rate linked to declining health in nonagenarians. Using FI34 as a quantitative phenotype, we have also found a genomic region on chromosome 12 that is associated with healthy aging and longevity.

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Section: Introductionmentioning

confidence: 99%

Quantitative measures of healthy aging and biological age

Kim

Jazwinski

2015

Healthy Aging Res

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“…Recently, an analysis of the association between 20 common CNVs not typically covered by commercial arrays and longevity in 222 senior American Caucasians with replication in 1283 community‐dwelling senior European Caucasians resulted in the identification of a deletion in the neurexin superfamily member CNTNAP4 on chromosome 16q23.1 that was inversely associated with survival to 80 years in women (Iakoubov et al ., 2013). Further investigation of CNVs in other gene members of the neurexin superfamily by the same group additionally led to the detection of a CNV in the CNTNAP2 gene on chromosome 7q35‐36.1 that negatively associated with healthy aging in octogenarian men (Iakoubov et al ., 2015). …”

Section: Introductionmentioning

confidence: 99%

Copy number variation associates with mortality in long‐lived individuals: a genome‐wide assessment

et al. 2015

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SummaryCopy number variants (CNVs) represent a significant source of genetic variation in the human genome and have been implicated in numerous diseases and complex traits. To date, only a few studies have investigated the role of CNVs in human lifespan. To investigate the impact of CNVs on prospective mortality at the extreme end of life, where the genetic component of lifespan appears most profound, we analyzed genomewide CNV data in 603 Danish nonagenarians and centenarians (mean age 96.9 years, range 90.0–102.5 years). Replication was performed in 500 long‐lived individuals from the Leiden Longevity Study (mean age 93.2 years, range 88.9–103.4 years). First, we assessed the association between the CNV burden of each individual (the number of CNVs, the average CNV length, and the total CNV length) and mortality and found a significant increase in mortality per 10 kb increase in the average CNV length, both for all CNVs (hazard ratio (HR) = 1.024, P = 0.002) and for duplications (HR = 1.011, P = 0.005), as well as per 100 kb increase in the total length of deletions (HR = 1.009, P = 0.0005). Next, we assessed the relation between specific deletions and duplications and mortality. Although no genome–wide significant associations were discovered, we identified six deletions and one duplication that showed consistent association with mortality in both or either of the sexes across both study populations. These results indicate that the genome–wide CNV burden, specifically the average CNV length and the total CNV length, associates with higher mortality in long‐lived individuals.

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“…DNA quantity was assessed by real time quantitative PCR using a ViiA™ 7 Real-Time PCR System (Life Technologies). Since Iakubov et al have found that the "at risk" variants are del/del for Esv12669 in the CNTNAP4 gene and for Esv11910 in CNTNAP2 gene the presence of ins allele, regular PCR is enough to discriminate between the presence of the insertion (ins/ins or ins/del) or its absence (del/del) (10,11). Variants of each CNVs were determined using a ViiA™ 7 Real-Time PCR System (Life Technologies) following the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…This correlation was observed in German patients; however, it was not evident in an Italian cohort (8,9). Interestingly, it was shown that some SNPs of CNTNAP2 and CNTNAP4 genes are associated with aging and age-related disorders such as Alzheimer's and Parkinson's diseases (10,11) There is increasing evidence that oxidative stress is involved in the pathobiology of PEX. Polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species (12,13).…”

Section: Prace Oryginalnementioning

confidence: 98%

“…A new association with systemic diseases and limited survival past 80 years was recently reported for a copy number variation (CNV) in the CNTNAP4 gene from the neurexin superfamily (10). Iakoubov et al have demonstrated associations between the CNTNAP4 gene and its esv12669 del/del polymorphic variant and longevity, healthy aging, as well as age-related pathologies such as cognitive impairment and, tentatively, Alzheimer's and Parkinson's diseases (11). We analyzed the association between CNTNAP4 esv12669 polymorphism with PEX and found no correlation with this disease.…”

Section: No Association Between Cntnap4 and Pexmentioning

confidence: 99%

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Genetic background analysis of pseudoexfoliation syndrome in Polish population – summary overview

Malukiewicz¹,

Lesiewska²,

Stafiej³

et al. 2019

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Aim: To evaluate Contactin Associated Protein-Like 2 (CNTNAP2), Contactin-Associated Protein-Like 4 (CNTNAP4), Lysyl Oxidase-Like Protein 1 (LOXL1) and superoxide dismutase 1 (SOD1) gene polymorphisms in patients with pseudoexfoliation syndrome (PEX). Material and methods: The study group consisted of 73 cataract patients with PEX and 111 controls with cataract but without PEX. Blood samples were obtained from each participant via peripheral venepuncture and genomic DNA was isolated according to the standard procedures. Genotypes of the CNTNAP4 esv12669 was determined using a commercially available assay. Previously reported chosen gene polymorphisms assessed by us in PEX patients were overviewed. Results: There was no difference in both allele and haplotype frequencies of single-nucleotide polymorphisms (SNPs) in CNT-NAP2 (rs2107856 and rs214138) and in SOD1 (rs10432782 and rs2070424) between PEX patients and controls. There was no difference in in frequencies of copy-number variations (CNVs) alleles esv12669 in the CNTNAP4 and esv11910 in the CNTNAP2 between PEX patients and controls. There were significant associations between PEX and SNPs in LOXL1-for the G allele of rs3825942 (p = 0.0047) and for the T allele of rs216541 (p = 0.021). The haplotype (GGT) consisting of all three risk alleles was significantly overrepresented (87.5%) in patients with PEX. Conclusions: our studies confirm a genetic basis for PEX with the significant association between the assessed LOXL1 SNPs and PEX in Polish population.

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A Common Copy Number Variation Polymorphism in the <b><i>CNTNAP2</i></b> Gene: Sexual Dimorphism in Association with Healthy Aging and Disease

Cited by 11 publications

References 26 publications

Quantitative measures of healthy aging and biological age

Quantitative measures of healthy aging and biological age

Copy number variation associates with mortality in long‐lived individuals: a genome‐wide assessment

Genetic background analysis of pseudoexfoliation syndrome in Polish population – summary overview

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