CONTEXT: Recently, it was proposed that a combination of the 83,557insA polymorphism in the 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) gene and the R453Q polymorphism in the hexose-6-phosphate dehydrogenase (H6PD) gene interacts to cause cortisone reductase deficiency (CRD) when at least three alleles are affected. OBJECTIVE: The aim was to study the separate and combined effects of these polymorphisms on body composition, adrenal androgen production, blood pressure, glucose metabolism, and the incidence of dementia in the healthy elderly population. DESIGN/SETTING/PARTICIPANTS: The Rotterdam study (n = 6105) and the Frail Old Men study (n = 347) are population-based cohort studies in the elderly. MAIN OUTCOME MEASURES: Genotype distributions and influences of (combined) genotypes on body mass index, adrenal androgen production, waist to hip ratio, systolic and diastolic blood pressure, fasting glucose levels, glucose tolerance test, and incidence of dementia were measured. RESULTS: No influence of the HSD11B1 83,557insA (allele frequencies 22.0 and 21.5%) and H6PD R453Q (allele frequencies 22.9 and 20.2%) variants was found for the different outcome measures that were investigated, either separately or when at least three alleles were affected. CONCLUSIONS: Two population-based studies among Caucasian elderly showed no evidence for (combined) effects of two polymorphisms in the HSD11B1 and H6PD genes on body composition, adrenal androgen production, blood pressure, glucose metabolism, and incidence of dementia. Moreover, the high frequencies observed for these two polymorphisms do not correspond to the low incidence of CRD observed in the general population. Altogether, it is unlikely that these polymorphisms cause CRD.

*Blood Pressure, *Body Composition, *Polymorphism, Single Nucleotide, 11-beta-Hydroxysteroid Dehydrogenases/*genetics, Adrenal Glands/metabolism, Aged, Androgens/*biosynthesis, Body Mass Index, Carbohydrate Dehydrogenases/*genetics, Cortisone Reductase/*deficiency, Dementia/enzymology/*genetics, Glucose/*metabolism, Humans, Male, Waist-Hip Ratio
dx.doi.org/10.1210/jc.2006-1349, hdl.handle.net/1765/14102
Journal of Clinical Endocrinology and Metabolism
Erasmus MC: University Medical Center Rotterdam

Smit, P, Dekker, M.J.H.J, de Jong, F.J, van den Beld, A.W, Koper, J.W, Pols, H.A.P, … Lamberts, S.W.J. (2007). Lack of Association of the 11beta-hydroxysteroid dehydrogenase type 1 gene 83,557insA and hexose-6-phosphate dehydrogenase gene R453Q polymorphisms with body composition, adrenal androgen production, blood pressure, glucose metabolism, and dementia. Journal of Clinical Endocrinology and Metabolism, 92(1), 359–362. doi:10.1210/jc.2006-1349