High penetrance, overweight, and glucocorticoid receptor variant: case-control study

A possible link between the glucocorticoid receptor gene ( GRL , 5q31-q32) and overweight has been suggested in a study of 42 families with morbid obesity.1 Data from another small study—of pairs of siblings—although not significant, showed a trend towards similar body mass index (weight(kg)/(height(m)2); difference=2.4) for 20 pairs sharing similar alleles compared with 19 pairs having discordant alleles (difference=3.5).2 An Asn363Ser variant, caused by a single nucleotide difference (A1218G) in exon 2 of GRL has since shown an association with increased sensitivity to glucocorticoids.3 Because of the predisposition to a rise in body mass index that this increased sensitivity should cause, we tested this variant for association with overweight in two groups of non-diabetic white subjects of British descent. All participants lived in or near Sydney and …