Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+)
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study and Participants
2.2. Selection of Genetic Loci and Genotyping Method
2.3. Questionnaire
2.4. Data Analysis
3. Results
3.1. Subjective General Health
3.2. Objective General Health
3.3. Multivariate Analysis
4. Discussion
5. Conclusions
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- The examined ten genetic loci involved in the cellular pathways of DNA damage repair showed a more significant association with the self-rated health and functional ability scores than with the number of diagnosed diseases or prescribed drugs.
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- Subjective and objective indicators of general health were almost entirely related to different genetic loci. Also, general cognitive function, as assessed by the MMSE score, was matched with subjective general health variables.
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- rs16847897 in the TERC gene showed the most significant relationships with both quantitative and qualitative subjective general health variables and was associated with all three aspects of self-assessments: health, mobility, and independence (as well as with the MMSE score). The more frequent GG homozygote of this genetic locus, which has been associated with longevity in previous studies, was consistently related to better scores.
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- The most significant relationship found between the binarised variable of functional ability (sum of self-rated mobility and independence) and rs16847897 in the TERC gene remained when an additional eight variables were included in the multivariate logistic regression model, indicating that the TERC locus investigated here might have a true impact on the overall vitality of the oldest-old people.
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- For a firm conclusion on the connection of vitality and health with cellular ageing, a much more extensive experimental design is needed (more SNP loci such as in GWAS), and the results need to be confirmed in other populations.
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SNP | Closest Gene | Chromosome Position (GRCh38) | Alleles (Major/Minor) | MAF | Genotyping Success Rate | HWE p-Value with Yates’s Correction * |
---|---|---|---|---|---|---|
rs225119 | PARK7 | 1:7984301 | C/T | 0.425 | 0.979 | 0.815 |
rs16847897 | TERC | 3:169850328 | G/C | 0.292 | 0.979 | 0.996 |
rs2706372 | RAD50/IL13 region | 5:132599785 | C/T | 0.272 | 0.960 | 0.997 |
rs1800795 | IL6 | 7:22727026 | G/C | 0.448 | 0.948 | 0.562 |
rs4977756 | CDKN2B/ANRIL | 9:22068653 | A/G | 0.399 | 0.966 | 0.959 |
rs1333049 | CDKN2A | 9:22125504 | G/C | 0.470 | 0.972 | 0.319 |
rs533984 | MRE11A | 11:94466106 | G/A | 0.396 | 0.960 | 0.589 |
rs17202060 | TXNRD1 | 12:104337068 | C/T | 0.336 | 0.960 | 0.812 |
rs1042522 | TP53 | 17:7676154 | C/G | 0.238 | 0.976 | 0.448 |
rs50871 | ERCC2 | 19:45359257 | A/C | 0.460 | 0.966 | 0.902 |
Gene (rsID) | p-Value ANOVA | Variables | Means in More Frequent Homozygotes | Means in Heterozygotes | Means in Less Frequent Homozygotes | Genotypes with Significant Differences | p-Value Post Hoc Test |
---|---|---|---|---|---|---|---|
TERC (rs16847897) | 0.001 | Sum: self-rated health AND mobility AND independence | 9.18 | 8.02 | 7.44 | GG:CC GG:GC | 0.005 0.001 |
0.005 | Sum: self-rated mobility AND independence | 6.35 | 5.59 | 5.30 | GG:CC GG:GC | 0.022 0.005 | |
0.005 | Sum: self-rated health AND self-rated health compared to that of their age peers AND mobility AND independence | 11.81 | 10.63 | 10.08 | GG:CC GG:GC | 0.018 0.006 | |
0.006 | Sum: self-rated health AND self-rated health compared to that of their age peers | 5.48 | 4.97 | 4.72 | GG:CC GG:GC | 0.019 0.007 | |
0.014 | MMSE | 23.34 | 21.61 | 23.74 | GC:CC GC:GG | 0.060 0.007 | |
MRE11A (rs533984) | 0.005 | Sum: self-rated mobility AND independence | 6.04 | 5.60 | 6.84 | AA:GA AA:GG | 0.001 0.044 |
0.016 | Sum: self-rated health AND mobility AND independence | 8.52 | 8.21 | 9.72 | AA:GA AA:GG | 0.004 0.028 | |
0.029 | Sum: self-rated health AND self-rated health compared to that of their age peers AND mobility AND independence | 11.13 | 10.82 | 12.45 | AA:GA AA:GG | 0.008 0.038 | |
CDKN2B (rs4977756) | 0.032 | Sum: self-rated health AND self-rated health compared to that of their age peers AND mobility AND independence | 10.60 | 11.28 | 12.22 | GG:AA | 0.010 |
0.046 | Sum: self-rated health AND mobility AND independence | 8.11 | 8.58 | 9.43 | GG:AA | 0.014 | |
TXNRD1 (rs17202060) | 0.024 | Number of drugs per day | 2.14 | 2.24 | 1.79 | TT:CC TT:TC | 0.033 0.006 |
0.038 | Number of diseases | 6.14 | 5.49 | 5.24 | CC:TC CC:TT | 0.030 0.046 | |
IL6 (rs1800795) | 0.028 | Number of drugs per day | 1.95 | 2.21 | 2.28 | GG:CC GG:GC | 0.018 0.025 |
PARK7 (rs225119) | 0.030 | Number of diseases | 5.65 | 5.53 | 6.54 | TT:CC TT:TC | 0.033 0.009 |
Gene (rsID) | Variables | Class Where the Genotype(s) Is More Frequent | More Frequent Genotype(s) | Minor Allele | p-Value |
---|---|---|---|---|---|
TERC (rs16847897) | Sum: self-rated mobility AND independence | 7–10 | GG | C | 0.00026 |
Self-rated health | good, very good, excellent | GG | C | 0.00133 | |
Sum: self-rated health AND mobility AND independence | 7–15 | GG | C | 0.00148 | |
Sum: self-rated health AND self-rated health compared to that of their age peers | 6–8 | GG | C | 0.004 | |
Self-rated mobility | good, very good, excellent | GG | C | 0.005 | |
Sum: self-rated health AND self-rated health compared to that of their age peers AND mobility AND independence | 10–18 | GG | C | 0.021 | |
Self-rated independence | good, very good, excellent | GG | C | 0.029 | |
MMSE score | 18+ | GG, CC | C | 0.010 | |
MRE11A (rs533984) | Sum: self-rated mobility AND independence | 7–10 | AA | A | 0.006 |
Self-rated independence | very good, excellent | AA, GG | A | 0.009 | |
Number of drugs per day/by median/ | 0–2 drugs per day | AA | A | 0.005 | |
CDKN2B (rs4977756) | Sum: self-rated health AND self-rated health compared to that of their age peers | 6–8 | GG | G | 0.013 |
Self-rated mobility | very good, excellent | GG | G | 0.018 | |
Self-rated independence | very good, excellent | GG, GA | G | 0.039 | |
CDKN2A (rs1333049) | Self-rated mobility | very good, excellent | GG | C | 0.031 |
PARK7 (rs225119) | Number of diseases | Men: 6–12; Women: 7–12 | TT | T | 0.034 |
RAD50 (rs2706372) | Number of diseases | Men: 6–12; Women: 7–12 | CC, TT | T | 0.026 |
TXNRD1 (rs17202060) | Number of drugs per day | 4+ (in both genders) | TC | T | 0.050 |
Variables | p-Value | OR | 95%CI |
---|---|---|---|
Gender (women are referent) | 0.399 | 1.319 | 0.694–2.507 |
Age at measurement (years) | 0.024 | 0.974 | 0.951–0.996 |
MMSE score | 0.001 | 1.125 | 1.053–1.203 |
Number of chronic diseases and conditions | 0.000 | 0.738 | 0.645–0.844 |
Number of drugs per day | 0.682 | 0.974 | 0.859–1.105 |
TERC (rs16847897) | 0.001 | ||
CC, GG are referent (vs. GC) | 0.851 | 0.900 | 0.300–2.702 |
CC, GC are referent (vs. GG) | 0.076 | 2.648 | 0.903–7.763 |
MRE11A (rs533984) | 0.002 | ||
GA, GG are referent (vs. AA) | 0.037 | 2.536 | 1.055–6.094 |
AA, GG are referent (vs. GA) | 0.066 | 0.566 | 0.309–1.038 |
CDKN2B (rs4977756) | 0.063 | ||
AA, GG are referent (vs. GA) | 0.994 | 1.002 | 0.502–2.003 |
AA, GA are referent (vs. GG) | 0.040 | 2.966 | 1.051–8.369 |
CDKN2A (rs1333049) | 0.439 | 1.051–8.369 | |
GC, GG are referent (vs. CC) | 0.543 | 1.340 | 0.522–3.445 |
CC, GG are referent (vs. GC) | 0.207 | 1.640 | 0.761–3.536 |
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Šetinc, M.; Zajc Petranović, M.; Slivšek, G.; Mijač, S.; Celinščak, Ž.; Stojanović Marković, A.; Bišof, V.; Peričić Salihović, M.; Škarić-Jurić, T. Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+). Genes 2023, 14, 1806. https://doi.org/10.3390/genes14091806
Šetinc M, Zajc Petranović M, Slivšek G, Mijač S, Celinščak Ž, Stojanović Marković A, Bišof V, Peričić Salihović M, Škarić-Jurić T. Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+). Genes. 2023; 14(9):1806. https://doi.org/10.3390/genes14091806
Chicago/Turabian StyleŠetinc, Maja, Matea Zajc Petranović, Goran Slivšek, Sandra Mijač, Željka Celinščak, Anita Stojanović Marković, Vesna Bišof, Marijana Peričić Salihović, and Tatjana Škarić-Jurić. 2023. "Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+)" Genes 14, no. 9: 1806. https://doi.org/10.3390/genes14091806
APA StyleŠetinc, M., Zajc Petranović, M., Slivšek, G., Mijač, S., Celinščak, Ž., Stojanović Marković, A., Bišof, V., Peričić Salihović, M., & Škarić-Jurić, T. (2023). Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+). Genes, 14(9), 1806. https://doi.org/10.3390/genes14091806