Endocrine Abstracts (2002) 3 P158

Lack of association between polymorphic markers within 11b-hydroxysteroid dehydrogenase type 1 gene (HSD11B1) and obesity

N Draper1, SM Echwald2, TIA Sorensen2,3, A Astrup3, GG Lavery1, SM Chalder1, M Hewison1, OB Pedersen2 & PM Stewart1

1Division of Medical Sciences, University of Birmingham, Birmingham, UK; 2Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Copenhagen, Denmark; 3Danish Epidemiology Science Centre, Institute of Preventive Medicine, Copenhagen University Hospital, Denmark.

11beta-hydroxysteroid dehydrogenase regulates glucocorticoid action, by interconverting cortisone (E) to cortisol (F). The Type 1 isozyme (11betaHSD1) is an oxoreductase expressed in adipose tissue, where it may play a role in the pathogenesis of visceral obesity.

We have characterised two polymorphic (CA)n microsatellite markers within intron 4 of the HSD11B1 gene, termed (CA)15 and (CA)19. In an earlier study evaluating a 'normal' population (MONICA cohort n=454) a weak association between increased 11betaHSD1 activity and increased W: Hratio with frequency of short alleles at the (CA)19 locus was observed. We have now analysed these markers in a larger, obese cohort.

The microsatellites, (CA)19 and (CA)15, were PCR amplified using fluorescent primers and genotyped on an ABI 377 DNA sequencer from DNA of 557 Danish men, aged 18 (AdiGEN cohort). These samples consisted of 323 control lean subjects and 234 obese subjects (BMI >31 Kg/m2). Genotypic data was compared with clinical markers of obesity (BMI, W: Hratio, waist circumference, fat mass, and cholesterol). There was no significant difference in the distribution of either microsatellite marker between lean and obese populations. Allele distributions were binomial and the data split accordingly as a function of the number of short alleles (0, 1 or 2 short alleles). No significant association was seen between grouped alleles and the clinical parameters (e.g mean BMI for the CA19 marker: 0 short alleles (36.1), 1 short (35.0), and 2 short (37.3)). No significant association between a single allele size and clinical parameter was observed (e.g mean BMI for CA19 marker: 0 short allele (35.9) vs 1 short allele (35.9)).

The absence of any association could be attributed to the low heterozgosity values of these markers (CA15 0.43 and CA19 0.47). Characterisation of novel markers within HSD11B1 will provide a better insight into the relationship between 11beta-hydroxysteroid dehydrogenase Type 1 and obesity.

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