Glucocorticoid receptor gene variant is associated with increased body fatness in youngsters.
OBJECTIVE
Sensitivity to glucocorticoids is known to be highly variable between individuals and is partly determined by polymorphisms in the glucocorticoid receptor (GR) gene. We investigated the relationship between four GR gene polymorphisms and body composition during puberty and at young adult age.


METHODS
An observational study with repeated measurements.


METHODS
Two comparable young Dutch cohorts with a generational difference of about 20 years were investigated. The first cohort consisted of 284 subjects born between 1961 and 1965. Measurements were performed from 13 to 36 years of age. The second cohort consisted of 235 subjects born between 1981 and 1989. Measurements were performed from 8 to 14 years of age.


METHODS
Associations between height, weight, BMI, fat mass (FM) and fat-free mass and four well-known functional polymorphisms were investigated. Results In boys in the younger cohort, the G-allele of the BclI polymorphism (haplotype 2) was associated with a higher body weight, weight-SDS, BMI, BMI-SDS and FM. These associations were not observed in the older cohort. Irrespective of genotype, the younger cohort showed a significantly higher total FM, body weight and BMI compared with the older cohort.


CONCLUSIONS
Because the associations between the G-allele of the BclI polymorphism in the GR gene and body FM in boys were only found in a healthy young population, but not in a comparable, generally leaner cohort from an older generation, it is suggested that carriers of this polymorphism are likely to be more vulnerable to fat accumulation in today's obesity promoting environment, than noncarriers.
Voorhoeve
Paul G
PG
Department of Pediatric Endocrinology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. p.voorhoeve@cwz.nl
van den Akker
Erica L T
EL
van Rossum
Elisabeth F C
EF
Koper
Jan W
JW
van Mechelen
Willem
W
Lamberts
Steven W J
SW
Delemarre-van de Waal
Henriette A
HA
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000293:Adolescent; D000328:Adult; D001823:Body Composition / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*
D011965:Receptors, Glucocorticoid