TY - JOUR
T1 - Genetic regulation of the variation of circulating insulin-like growth factors and leptin in human pedigrees
AU - Pantsulaia, Ia
AU - Trofimov, Svetlana
AU - Kobyliansky, Eugene
AU - Livshits, Gregory
N1 - Funding Information:
This study was supported jointly by grant 1042/04 from the Israel National Science Foundation, by grant 112-551 from Tel Aviv University, Tel Aviv, Israel (Livshits and Kobyliansky), and by a postdoctoral fellowship grant to Pantsulaia, kindly provided by UNESCO and Israel (the Ministry of Education, the Council for Higher Education's Planning and Budgeting Committee, the Ministry of Foreign Affairs, and the Israel National Commission for UNESCO).
PY - 2005/7
Y1 - 2005/7
N2 - Recent literature has shown that circulating levels of insulin-like growth factor I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk assessment of several chronic diseases including cancer, cardiovascular disease, diabetes mellitus and so on. The present study examined the extent of genetic and environmental influences on the populational variation of circulating IGF-I and IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative genetic analysis showed that the IGF-I variation was appreciably attributable to genetic effects (47.1% ± 9.0%), whereas for IGF-BP-1, only 23.3% ± 7.8% of the interindividual variation was explained by genetic determinants. Common familial environment factors contributed significantly only to IGF-BP-1 variation (23.3% ± 7.8%). In addition, we examined the covariations between these molecules and between them and IGF-BP-3 and leptin that were previously studied in the same sample. The analysis revealed that the pleiotropic genetic effects were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 ± 0.04 and 0.15 ± 0.05. The common environmental factors were consistently a significant source of correlation between all pairs (barring IGF-I and leptin) of the studied molecules; they were the sole predictors of correlation between IGF-I and IGF-BP-1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of specific and common genetic pathways that in combination determine a substantial proportion of the circulating variation of these molecules.
AB - Recent literature has shown that circulating levels of insulin-like growth factor I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk assessment of several chronic diseases including cancer, cardiovascular disease, diabetes mellitus and so on. The present study examined the extent of genetic and environmental influences on the populational variation of circulating IGF-I and IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative genetic analysis showed that the IGF-I variation was appreciably attributable to genetic effects (47.1% ± 9.0%), whereas for IGF-BP-1, only 23.3% ± 7.8% of the interindividual variation was explained by genetic determinants. Common familial environment factors contributed significantly only to IGF-BP-1 variation (23.3% ± 7.8%). In addition, we examined the covariations between these molecules and between them and IGF-BP-3 and leptin that were previously studied in the same sample. The analysis revealed that the pleiotropic genetic effects were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 ± 0.04 and 0.15 ± 0.05. The common environmental factors were consistently a significant source of correlation between all pairs (barring IGF-I and leptin) of the studied molecules; they were the sole predictors of correlation between IGF-I and IGF-BP-1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of specific and common genetic pathways that in combination determine a substantial proportion of the circulating variation of these molecules.
UR - http://www.scopus.com/inward/record.url?scp=20444447189&partnerID=8YFLogxK
U2 - 10.1016/j.metabol.2005.02.014
DO - 10.1016/j.metabol.2005.02.014
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C2 - 15988710
AN - SCOPUS:20444447189
SN - 0026-0495
VL - 54
SP - 975
EP - 981
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 7
ER -
