Alu Deletions in <i>LAMA2</i> and <i>CDH4</i> Genes Are Key Components of Polygenic Predictors of Longevity
Longevity is a unique human phenomenon and a highly stable trait, characterized by polygenicity. The longevity phenotype occurs due to the ability to successfully withstand the age-related genomic instability triggered by Alu elements. The purpose of our cross-sectional study was to evaluate the com...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/21/13492 |
| Summary: | Longevity is a unique human phenomenon and a highly stable trait, characterized by polygenicity. The longevity phenotype occurs due to the ability to successfully withstand the age-related genomic instability triggered by Alu elements. The purpose of our cross-sectional study was to evaluate the combined contribution of <i>ACE*Ya5ACE</i>, <i>CDH4*Yb8NBC516</i>, <i>COL13A1</i>*<i>Ya5ac1986</i>, <i>HECW1*Ya5NBC182</i>, <i>LAMA2*Ya5-MLS19</i>, <i>PLAT*TPA25</i>, <i>PKHD1L1*Yb8AC702</i>, <i>SEMA6A*Yb8NBC597</i>, <i>STK38L*Ya5ac2145</i> and <i>TEAD1*Ya5ac2013</i> Alu elements to longevity. The study group included 2054 unrelated individuals aged from 18 to 113 years who are ethnic Tatars from Russia. We analyzed the dynamics of the allele and genotype frequencies of the studied Alu polymorphic loci in the age groups of young (18–44 years old), middle-aged (45–59 years old), elderly (60–74 years old), old seniors (75–89 years old) and long-livers (90–113 years old). Most significant changes in allele and genotype frequencies were observed between the long-livers and other groups. The search for polygenic predictors of longevity was performed using the APSampler program. Attaining longevity was associated with the combinations <i>LAMA2*ID + CDH4*D</i> (OR = 2.23, P<sub>Bonf</sub> = 1.90 × 10<sup>−2</sup>) and <i>CDH4*DD + LAMA2*ID + HECW1*D</i> (OR = 4.58, P<sub>Bonf</sub> = 9.00 × 10<sup>−3</sup>) among persons aged between 18 and 89 years, <i>LAMA2</i>*<i>ID + CDH4*D + SEMA6A*I</i> for individuals below 75 years of age (OR = 3.13, P<sub>Bonf</sub> = 2.00 × 10<sup>−2</sup>), <i>LAMA2*ID + HECW1*I</i> for elderly people aged 60 and older (OR = 3.13, P<sub>Bonf</sub> = 2.00 × 10<sup>−2</sup>) and <i>CDH4*DD + LAMA2*D + HECW1*D</i> (OR = 4.21, P<sub>Bonf</sub> = 2.60 × 10<sup>−2</sup>) and <i>CDH4*DD + LAMA2*D + ACE*I</i> (OR = 3.68, P<sub>Bonf</sub> = 1.90 × 10<sup>−2</sup>) among old seniors (75–89 years old). The key elements of combinations associated with longevity were the deletion alleles of <i>CDH4</i> and <i>LAMA2</i> genes. Our results point to the significance for human longevity of the Alu polymorphic loci in <i>CDH4</i>, <i>LAMA2</i>, <i>HECW1</i>, <i>SEMA6A</i> and <i>ACE</i> genes, involved in the integration systems. |
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| ISSN: | 1661-6596 1422-0067 |