Functional analysis of polymorphic insertions of Alu retroelements in acute lymphoblastic leukemia patients

Komkov, Alexander; Maschan, Michael; Швец, В. И.; Lebedev, Yuri B.

doi:10.1134/s1068162012030089

Cited by 7 publications

(2 citation statements)

References 27 publications

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“…In two identified patterns, the presence of the LAMA2*D allele provided the long-livers with an advantage over old individuals aged under 90 years. Bearing in mind the inhibitory effect of Alu insertions on the expression of genes containing them [ 50 ], it is likely that a moderate and elevated level of laminin-2 is associated with longevity.…”

Section: Discussionmentioning

confidence: 99%

Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity

Erdman

Каримов

Tuktarova

et al. 2022

IJMS

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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 ACE*Ya5ACE, CDH4*Yb8NBC516, COL13A1*Ya5ac1986, HECW1*Ya5NBC182, LAMA2*Ya5-MLS19, PLAT*TPA25, PKHD1L1*Yb8AC702, SEMA6A*Yb8NBC597, STK38L*Ya5ac2145 and TEAD1*Ya5ac2013 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 LAMA2*ID + CDH4*D (OR = 2.23, PBonf = 1.90 × 10−2) and CDH4*DD + LAMA2*ID + HECW1*D (OR = 4.58, PBonf = 9.00 × 10−3) among persons aged between 18 and 89 years, LAMA2*ID + CDH4*D + SEMA6A*I for individuals below 75 years of age (OR = 3.13, PBonf = 2.00 × 10−2), LAMA2*ID + HECW1*I for elderly people aged 60 and older (OR = 3.13, PBonf = 2.00 × 10−2) and CDH4*DD + LAMA2*D + HECW1*D (OR = 4.21, PBonf = 2.60 × 10−2) and CDH4*DD + LAMA2*D + ACE*I (OR = 3.68, PBonf = 1.90 × 10−2) among old seniors (75–89 years old). The key elements of combinations associated with longevity were the deletion alleles of CDH4 and LAMA2 genes. Our results point to the significance for human longevity of the Alu polymorphic loci in CDH4, LAMA2, HECW1, SEMA6A and ACE genes, involved in the integration systems.

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Section: Discussionmentioning

confidence: 99%

Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity

Erdman

Каримов

Tuktarova

et al. 2022

IJMS

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“…However, abnormal regulation of their retrotransposon activities often leads to many diseases (5). The Human Genetic Mutation Database illustrated that Alu elements are associated with approximately 0.1% of human genetic diseases (5), including neurofibromatosis (6), leukemia (7), Alzheimer’s disease (8), and breast cancer (9). These diseases are caused by inappropriate insertions of Alu elements in the coding regions of the respective causative genes.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into stress granules

Hwang

Baek

et al. 2019

BMB Rep.

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The Alu element, the most abundant transposable element, is transcribed to Alu RNA. We hypothesized that the PIWI protein regulates the expression of Alu RNA in retinal pigment epithelial (RPE) cells, where accumulated Alu RNA leads to macular degeneration. Alu transcription was induced in RPE cells treated with H 2 O 2 . At an early stage of oxidative stress, PIWIL4 was translocated into the nucleus; however, subsequently it was sequestered into cytoplasmic stress granules, resulting in the accumulation of Alu RNA. An elevated amount of Alu RNA was positively correlated with the disruption of the epithelial features of RPE via induction of mesenchymal transition. Therefore, we suggest that oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into the cytoplasmic stress granules.

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Gene polymorphisms and oral cancer risk in tobacco habitués

2015

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Oral cancer incidence of 77,003 poses a major health concern in India, with 5-10 % tobacco habitués developing oral cancer. The current study examined the role of specific genomic variants in oral cancer. We examined five genomic variants represented as single nucleotide polymorphisms (SNPs) in genes associated with cell proliferation and cellular invasion. The SNPs rs2124437 (RASGRP3), rs1335022 (GRIK2), rs4512367 (PREX2), rs4748011 (CCDC3), and rs1435218 (LNX1) were analyzed in 500 histopathologically confirmed oral cancers and 500 healthy controls with a minimum of 10 years of tobacco usage. Allelic discrimination real-time PCR SYBR Green assay was used. The genotypic and allelic frequencies between cases and controls were analyzed using SPSS software (version 19) and odds ratio (OR) using Hutchon.net, indicating increased risk to oral cancers. A significant association of the SNPs in oral cancer was observed in RASGRP3 AA (rs2124437) (p < 0.000, OR 1.34, 95 % confidence interval (CI) 1.01-1.76), GRIK2 TT (rs1335022) (p = 0.008, OR 1.58, 95 % CI 1.23-2.03), PREX2 CC (p = 0.008, OR 1.56, 95 % CI 1.15-2.1), and TT (p < 0.000, OR 2.77, 1.68-4.57) genotypes, whereas the heterozygous genotypes showed higher frequencies in controls, i.e., GRIK2 CT (rs1335022) (p = 0.029, OR 0.68, 95 % CI 0.53-0.87) and PREX2 CT (p = 0.004, OR 0.49, 95 % CI 0.37-0.64), indicating protection. Coinheritance of the SNPs was associated with further increase in the risk. Thus, the SNP genotypes in the three genes, present singly or as a coinherited panel constituted "Predictive Biomarkers" indicating increased risk of oral cancer in tobacco habitués.

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Functional analysis of polymorphic insertions of Alu retroelements in acute lymphoblastic leukemia patients

Cited by 7 publications

References 27 publications

Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity

Alu Deletions in LAMA2 and CDH4 Genes Are Key Components of Polygenic Predictors of Longevity

Oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into stress granules

Gene polymorphisms and oral cancer risk in tobacco habitués

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