A common polymorphism in the UCP3 promoter influences hand grip strength in elderly people

Crocco, Paolina; Montesanto, Alberto; Passarino, Giuseppe; Rose, Giuseppina

doi:10.1007/s10522-011-9321-z

Cited by 19 publications

(18 citation statements)

References 51 publications

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“…Overall, only 2 of the top 14 genes found associated with functional status in this work have been previously reported in association studies with physical status at old age, in Italian and Danish Cohorts (the latter is the same used in the present paper), and they belong to UCPs family (Crocco et al, 2011; Dato et al, 2012b). Both UCP2 and UCP3 confirmed to have a major effect on physical tests such as HG and WS in the whole sample, as well as in the two gender separately, with the rs11235972 influencing the survival at old age too.…”

Section: Discussionmentioning

confidence: 75%

Contribution of genetic polymorphisms on functional status at very old age: A gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway

Dato¹,

Soerensen²,

Lagani³

et al. 2014

Experimental Gerontology

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Preservation of functional ability is a well-recognized marker of longevity. At a molecular level, a major determinant of the physiological decline occurring with aging is the imbalance between production and accumulation of oxidative damage to macromolecules, together with a decreased efficiency of stress response to avoid or repair such damage. In this paper we investigated the association of 38 genes (311 SNPs) belonging to the pro–antioxidant pathways with physical and cognitive performances, by analyzing single SNP and gene-based associations with Hand Grip strength (HG), Activities of Daily Living (ADL), Walking Speed (WS), Mini Mental State Examination (MMSE) and Composite Cognitive Score (CCS) in a Cohort of 1089 Danish nonagenarians. Moreover, for each gene analyzed in the pro–antioxidant pathway, we tested the influence on longitudinal survival. In the whole sample, nominal associations were found for TXNRD1 variability with ADL and WS, NDUFS1 and UCP3 with HG and WS, GCLC and UCP2 with WS (p < 0.05). Stronger associations although not holding the multiple comparison correction, were observed between MMSE and NDUFV1, MT1A and GSTP1 variability (p < 0.009). Moreover, we found that association between genetic variability in the pro–antioxidant pathway and functional status at old age is influenced by sex. In particular, most significant associations were observed in nonagenarian females, between HG scores and GLRX and UCP3 variability, between ADL levels and TXNRD1, MMSE and MT1A genetic variability. In males, a borderline statistically significant association with ADL level was found for UQCRFS1 gene. Nominally significant associations in relation to survival were found in the female sample only with SOD2, NDUFS1, UCP3 and TXNRD1 variability, the latter two confirming previous observations reported in the same cohort. Overall, our work supports the evidence that genes belonging to the pro–anti-oxidant pathway are able to modulate physical and cognitive performance after the ninth decade of life, finally influencing extreme survival.

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Section: Discussionmentioning

confidence: 75%

Contribution of genetic polymorphisms on functional status at very old age: A gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway

Dato¹,

Soerensen²,

Lagani³

et al. 2014

Experimental Gerontology

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“…Other SNPs in UCP3 are associated with childhood obesity and hand-grip strength (Crocco et al 2011; Dato et al 2012; Musa et al 2012). The LD block 2 in which rs1626521 belongs contains seven miRNA target sites as well as a missense variant rs8179179 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians

et al. 2016

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Energy expenditure decreases with age, but in the oldest-old, energy demand for maintenance of body functions increases with declining health. Uncoupling proteins have profound impact on mitochondrial metabolic processes; therefore, we focused attention on mitochondrial uncoupling protein genes. Alongside resting metabolic rate (RMR), two SNPs in the promoter region of UCP2 were associated with healthy aging. These SNPs mark potential binding sites for several transcription factors; thus, they may affect expression of the gene. A third SNP in the 3′-UTR of UCP3 interacted with RMR. This UCP3 SNP is known to impact UCP3 expression in tissue culture cells, and it has been associated with body weight and mitochondrial energy metabolism. The significant main effects of the UCP2 SNPs and the interaction effect of the UCP3 SNP were also observed after controlling for fat-free mass (FFM) and physical-activity related energy consumption. The association of UCP2/3 with healthy aging was not found in males. Thus, our study provides evidence that the genetic risk factors for healthy aging differ in males and females, as expected from the differences in the phenotypes associated with healthy aging between the two sexes. It also has implications for how mitochondrial function changes during aging.

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“…For replication of prior GS-associated SNPs, the appropriate genetic model was used as previously described in the literature: recessive for SNPs from CNTF (Arking et al 2006) and UCP3 (Crocco et al 2011;Dato et al 2012b) or dominant for IL15 SNPs (Dato et al 2010). Even though single SNP tests for association within the genes may not be independent due to linkage disequilibrium (LD), a conservative threshold of p=0.00625 (p=0.05/ 8) was set for significance, since we tested eight individual SNPs.…”

Section: Replication Of Prior Candidate Snp Resultsmentioning

confidence: 99%

“…The selected SNPs included two SNPs from UCP3 (rs1800849, rs11235972) (Crocco et al 2011;Dato et al 2012b) and two SNPS from IL15 (rs3806798, rs1519551) (Dato et al 2010). In addition, four SNPs, rs948562, rs1800169, rs550942 and rs4319530, from the CNTF gene were chosen as they covered the variation in a haplotype region previously associated with GS (Arking et al 2006).…”

Section: Candidate Snp Selectionmentioning

confidence: 99%

“…They include genes related to muscle catabolism, growth factors, cellular damage, hormonal regulation, vitamin D and collagen. Several studies reported positive association of variants in specific genes, including uncoupling protein 3 (UCP3) (Crocco et al 2011;Dato et al 2012b), which is involved in skeletal muscle catabolism; insulin-like growth factor-2 (IGF2) (Sayer et al 2002), involved in regulating muscle growth; and angiotensin-converting enzyme (ACE) (Yoshihara et al 2009), whose protein product not only regulates blood pressure but is also a skeletal muscle growth factor. Most of these results, however, have only been reported once, are subject to publication bias (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Genetics of hand grip strength in mid to late life

Chan

Thalamuthu

Oldmeadow

et al. 2015

AGE

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Hand grip strength (GS) is a predictor of mortality in older adults and is moderately to highly heritable, but no genetic variants have been consistently identified. We aimed to identify single nucleotide polymorphisms (SNPs) associated with GS in middle-aged to older adults using a genome-wide association study (GWAS). GS was measured using handheld dynamometry in community-dwelling men and women aged 55-85 from the Hunter Community Study (HCS, N = 2088) and the Sydney Memory and Ageing Study (Sydney MAS, N = 541). Genotyping was undertaken using Affymetrix microarrays with imputation to HapMap2. Analyses were performed using linear regression. No genome-wide significant results were observed in HCS nor were any of the top signals replicated in Sydney MAS. Gene-based analyses in HCS identified two significant genes (ZNF295, C2CD2), but these results were not replicated in Sydney MAS. One out of eight SNPs previously associated with GS, rs550942, located near the CNTF gene, was significantly associated with GS (p = 0.005) in the HCS cohort only. Study differences may explain the lack of consistent results between the studies, including the smaller sample size of the Sydney MAS cohort. Our modest sample size also had limited power to identify variants of small effect. Our results suggest that similar to various other complex traits, many genetic variants of small effect size may influence GS. Future GWAS using larger samples and consistent measures may prove more fruitful at identifying genetic contributors for GS in middle-aged to older adults.

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A common polymorphism in the UCP3 promoter influences hand grip strength in elderly people

Cited by 19 publications

References 51 publications

Contribution of genetic polymorphisms on functional status at very old age: A gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway

Contribution of genetic polymorphisms on functional status at very old age: A gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway

Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians

Genetics of hand grip strength in mid to late life

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