title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  The Rotterdam study (n = 6105) and the Frail Old Men study (n = 347) are population-based cohort studies in the elderly.
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine, Room Ee530C, Erasmus Medical Center, Dr. Molewaterplein 40, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Smit
authors.forename: Marieke J H J
authors.initials: MJ
authors.lastname: Dekker
authors.forename: Frank Jan
authors.initials: FJ
authors.lastname: de Jong
authors.forename: Annewieke W
authors.initials: AW
authors.lastname: van den Beld
authors.forename: Jan W
authors.initials: JW
authors.lastname: Koper
authors.forename: Huibert A P
authors.initials: HA
authors.lastname: Pols
authors.forename: Albert O
authors.initials: AO
authors.lastname: Brinkmann
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000311:Adrenal Glands / Q000378:metabolism; D000368:Aged; D000728:Androgens / Q000096:biosynthesis*; D001794:Blood Pressure; D001823:Body Composition; D015992:Body Mass Index; D002237:Carbohydrate Dehydrogenases / Q000235:genetics*; D003349:Cortisone Reductase / Q000172:deficiency*; D003704:Dementia / Q000201:enzymology / Q000235:genetics*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D049629:Waist-Hip Ratio
chemical_list: D000728:Androgens; D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003349:Cortisone Reductase; D005947:Glucose