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Heritability of susceptibility to ionizing radiation-induced apoptosis of human lymphocyte subpopulations.

Authors :
Schmitz A
Bayer J
Dechamps N
Goldin L
Thomas G
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.

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