Comments(1)

Human obesity and glucocorticoid receptor polymorphisms

Akheel Ahmed Syed   (01 September 2006)  Royal Victoria Infirmary

We read the paper by Marti et al [1] with great interest and offer the following comments. The allele frequency of the N363S polymorphism of the glucocorticoid receptor gene (GRL) in people of south Asian origin living in north-east England was 0.3% [2], not 0.7% as quoted by Marti et al. Interestingly, this polymorphism was not detected in a study involving 265 Japanese subjects [3]. Thus, in contrast to its higher frequency in people of European origin, the N363S polymorphism appears to occur very infrequently in Asians. Apart from ethnic differences, other polymorphisms with opposing effects may have influenced the results of the meta-analysis by Marti et al. For instance, the A3669G polymorphism in exon 9beta of GRL, which occurs at greater frequency (17%) than N363S, is associated with reduced central adiposity in Europid women [4]. Besides, the various published studies of the N363S polymorphism were from very different populations, and some from highly selected cohorts. Statistical analysis cannot control for differences in genetic background between populations. This in itself constitutes a fundamental flaw of meta-analysis. Thus, the biological effects of individual polymorphisms have to be interpreted in the context of the population studied – lack of concordance between studies does not negate the findings of individual studies.

References

1. Marti A, Ochoa MC, Sanchez-Villegas A, Martinez JA, Martinez-Gonzalez MA, et al. (2006) Meta-analysis on the effect of the N363S polymorphism of the glucocorticoid receptor gene (GRL) on human obesity. BMC Med Genet 7: 50.

2. Syed AA, Irving JA, Redfern CPF, Hall AG, Unwin NC, et al. (2004) Low prevalence of the N363S polymorphism of the glucocorticoid receptor in South Asians living in the United Kingdom. J Clin Endocrinol Metab 89: 232-235.

3. Koyano S, Saito Y, Sai K, Kurose K, Ozawa S, et al. (2005) Novel genetic polymorphisms in the NR3C1 (glucocorticoid receptor) gene in a Japanese population. Drug Metab Pharmacokinet 20: 79-84.

4. Syed AA, Irving JA, Redfern CPF, Hall AG, Unwin NC, et al. (2006) Association of glucocorticoid receptor polymorphism A3669G in exon 9beta with reduced central adiposity in women. Obesity (Silver Spring) 14: 759-764.

Akheel A. Syed, MRCP; Royal Victoria Infirmary

Jolanta U. Weaver, PhD, FRCP; University of Newcastle

Christopher P. F. Redfern, PhD; University of Newcastle

Newcastle upon Tyne

Competing interests

None

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