title: Common variation at the 11-β hydroxysteroid dehydrogenase type 1 gene is associated with left ventricular mass.
abstract: BACKGROUND
  Polymorphisms in 11-β hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) have been reported to be associated with obesity-related cardiovascular risk factors, such as type II diabetes and hypertension. Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular death associated with these factors but has significant additional heritability, the cause of which is undetermined. The 11β-HSD1 is believed to maintain tonic inhibition of the mineralocorticoid receptor in cardiomyocytes, and mineralocorticoid receptor activation is involved in the pathophysiology of LVH. We assessed the association between polymorphisms in the HSD11B1 gene and left ventricular mass (LVM) in 248 families ascertained through a proband with hypertension.
  
  
  RESULTS
  LVM was measured by electrocardiography and echocardiography in 868 and 829 participants, respectively. Single-nucleotide polymorphisms (SNPs) tagging common variation in the HSD11B1 gene were genotyped by mass spectrometry. The rs846910 SNP, which lies in the flanking region 5' to exon 1B of HSD11B1, was associated with LVM both by electrocardiography (≈5% lower LVM per copy of the rare allele, P=0.02) and by echocardiography (≈10% lower LVM per copy of the rare allele, P=0.003). Genotype explained 1% to 2% of the population variability in LVM, or approximately 5% of the heritable fraction. There were no significant associations between any HSD11B1 SNP and blood pressure or body mass index that could have confounded the association with LVM.
  
  
  CONCLUSIONS
  Genotype at HSD11B1 has a small, but significant effect on LVM, apparently independently of any effect on obesity-related traits. These findings suggest a novel action of 11β-HSD1 in the human cardiomyocyte, which may be of therapeutic importance.
authors.affiliation: Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Thahira J
authors.initials: TJ
authors.lastname: Rahman
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
authors.forename: Darroch
authors.initials: D
authors.lastname: Hall
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Avery
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: John M C
authors.initials: JM
authors.lastname: Connell
authors.forename: Hugh
authors.initials: H
authors.lastname: Watkins
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018161:Receptors, Mineralocorticoid / Q000737:chemistry / Q000378:metabolism; D012307:Risk Factors
chemical_list: D018161:Receptors, Mineralocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human