Functional Implication of an ARG307GLY Substitution in Corticosteroid Binding Globulin, a Candidate Gene for a QTL Associated with Cortisol Variability and Obesity
Veronique Guyonnet-Duperat 1, Nicoline Geverink 2, Graham S Plastow 3, Gary Evans 3, Olga Ousova 2, Christian Croisetiere 2, Aline Foury 2, Elodie Richard 2, Pierre Mormede 2 and Marie-Pierre Moisan 2*
1 Inserm
2 INRA
3 Sygen Int.
* To whom correspondence should be addressed. E-mail: m.moisan{at}imb.uq.edu.au.
Submitted on November 30, 2005
Revised on April 10, 2006
Accepted on 9 May 2006
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Abstract |
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In a previous study we reported that corticosteroid-binding globulin gene (Cbg) may be the causal gene of a quantitative trait locus associated with cortisol levels, fat deposition and muscle content in a pig intercross. Sequence analysis of parental animals allowed us to identify four amino-acid substitutions (Ser15Ile, Thr257Met, Ile265Val, Arg307Gly). Here, we have examined if any of these single amino acid substitutions could be responsible for the difference in CBG binding and affinity for cortisol between the parental breeds, using in vitro assays of Cbg variants (created by site-directed mutagenesis) after transfection of mammalian cells. Additionally, the Cbg coding region was analysed in samples from a synthetic pig line in order to study association between polymorphism and CBG biochemical properties, carcass composition and meat quality. Both in vitro transfection assays and the association studies suggest a role of the Arg307Gly mutation in increasing CBG capacity (by more than 70%) and decreasing CBG affinity for cortisol (by 30%). The Ile265Val substitution may also have an effect on decreasing CBG affinity for cortisol by 25%. The mutations Ser15Ile and Thr257Met do not seem to have an effect on CBG parameters. The Arg307Gly substitution was the only mutation associated with a parameter of meat quality (driploss) and no mutation was linked to carcass composition. In conclusion, the Arg307Gly substitution in Cbg is an important component of CBG variation and also for meat quality although other as yet unknown mutations probably explain the influence of CBG on fat deposition.
Key Words:
QTL, corticosteroid binding globulin, glucocorticoids, obesity, pig
