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Heritability of susceptibility to ionizing radiation-induced apoptosis of human lymphocyte subpopulations.
- Source :
-
International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2007 Jul 15; Vol. 68 (4), pp. 1169-77. - Publication Year :
- 2007
-
Abstract
- Purpose: To evaluate the heritability of intrinsic radiosensitivity, the induction of apoptosis in lymphocyte subpopulations was determined on samples from related individuals belonging to large kindred families.<br />Methods and Materials: Quiescent lymphocytes from 334 healthy individuals were gamma-irradiated in vitro. Apoptosis was determined 18 h after irradiation by eight-color flow cytometry. Radiosensitivity was quantified from dose-effect curves. Intrafamilial correlations and heritability were computed for 199 father-mother-offspring trios using the programs SOLAR (Sequential Oligogenic Linkage Analysis Routines) and SAGE (Statistical Analysis for Genetic Epidemiology). Segregation analyses were conducted using SAGE.<br />Results: Marked differential susceptibility of naive and memory T lymphocytes was demonstrated. Also, although age and gender were significant covariates, their effects only accounted for a minor part of the inter-individual variation. Parent-offspring and sib-sib correlations were significant for the radiosensitivity of B cells, T4, and T8 and of effector memory T4 and T8 subpopulations. In the T4-effector memory subpopulation, the phenotype showed correlations most consistent with dominant or additive genetic effects, and the results of the segregation analysis were consistent with the contribution of a bi-allelic dominant locus.<br />Conclusions: Heritability was demonstrated for the susceptibility to ionizing radiation-induced apoptosis of lymphocyte populations, and the segregation of the T4-effector memory radiosensitivity phenotype was consistent with a simple mendelian transmission model involving one major gene.
- Subjects :
- Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Dose-Response Relationship, Radiation
Female
Humans
Male
Middle Aged
Phenotype
Sex Factors
Siblings
Spouses
Apoptosis genetics
B-Lymphocytes radiation effects
CD4-Positive T-Lymphocytes radiation effects
CD8-Positive T-Lymphocytes radiation effects
Radiation Tolerance genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0360-3016
- Volume :
- 68
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of radiation oncology, biology, physics
- Publication Type :
- Academic Journal
- Accession number :
- 17637392
- Full Text :
- https://doi.org/10.1016/j.ijrobp.2007.03.050