Steroid receptor gene variant impacts metabolic health

By Sally Robertson, B.Sc.Jul 10 2012

A variant in the glucocorticoid receptor gene may be associated with increased body fat and insulin resistance, show study findings.

The BCLI polymorphism was associated with greater abdominal obesity and its metabolic consequences in a data analysis of 1228 participants, according to findings presented at the Endocrinology Society's annual meeting ENDO 2012 in Houston, Texas, USA.

"Our findings support the idea that even small variations in hormone receptor sensitivity can have metabolic implications, such as obesity or diabetes," said lead author Bastiaan Havekes, from Maastricht University Medical Center in The Netherlands, in a press statement.

Genotyping for the BCLI polymorphism among the participants (23% with pre-diabetes, 33% with diabetes), showed that 42% were noncarriers (CC), 44% were heterozygous (CG), and 14% were homozygous carriers (GG) of the G-allele.

Linear regression analysis showed that individuals with the GG genotype had a significantly higher body mass index and waist and hip circumference than those with the CC and CG genotype, after adjustment for gender, age, glucose metabolism, smoking, and use of medication.

These individuals also had significantly greater homeostatic model assessment of insulin resistance (HOMA-IR) than those with the CC and CG genotype.

This small variant makes the receptor more sensitive to glucocorticoids, resulting in greater effects with similar hormone levels, said Havekes. This excess exposure can result in weight gain, particularly around the abdominal region, and also disrupts glycemic control.

"Endocrinologists should not just focus on hormone levels themselves," warned Havekes. "Taking into account hormone receptor sensitivity could help in better understanding hormone-mediated effects on metabolism."

He pointed out that determining an individual's genetic risk profile for metabolic disease is of paramount importance to prevent development of cardiovascular diseases.

"Future studies concerning cardiovascular risk profiling should perhaps consider the BCLI polymorphism."

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