A polymorphism in the inhibin alpha-subunit gene is associated with bone mineral density (BMD) and serum inhibin b (INH b) concentrations in men
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1
St Thomas' Hospital, Department of Clinical Chemistry, United Kingdom
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2
Guy's Hospital, Osteoporosis Clinic, United Kingdom
{BR}Osteoporosis is a common complex polygenic disorder. However, the genes identified so far explain only a small proportion of the total genetic variation. New pathways may be implicated, particularly in men. The endocrine pathway involving the inhibins may be of importance. The inhibin alpha-subunit (INH-alpha) gene is proposed as a candidate gene because of its role in a feedback loop with sex hormones and gonadotrophins and its direct effect on bone remodelling. The aim of the study was to investigate the possible association between a polymorphic variant in the INH-alpha gene with BMD and circulating inh B in men. {BR}We studied 146 men aged mean [SD] 57 [13.7] years, 54 with osteoporosis and 92 controls. The polymorphism -16C>T in the 5'UTR of INH-alpha gene was screened in all subjects. BMD was measured at lumbar spine (LS), femoral neck (FN) and total hip (TH). Serum concentrations of FSH, LH, testosterone, inh B were determined. {BR}The prevalence of CC was 60%, CT: 37% and TT: 3%. After correction for age, height, weight and risk factors such as smoking habits, alcohol intake, exercise, dietary calcium intake , previous fracture, we found a significant independent association between INH-alpha genotype and BMD at the LS (p= 0.042). Z- score at the LS was lower in subjects with 'CT' and 'TT' genotype compared to 'CC' ( mean [SEM] ; CT/TT : - 1.03 [0.17], CC : -0.5[0.21] p=0.08). In a multi-linear regression model, which included the gonadotrophins and serum testosterone, INH-alpha genotype was found to be independently associated with serum inh B (p= 0.043). Subjects with the 'CC' genotype had higher serum inh B concentrations compared to 'CT' and 'TT' genotypes (mean [SEM]; CC: 129.8 [9.34], CT/TT: 106 [8.4] pg/ml, p=0.06). {BR}These preliminary data suggest that INH-alpha gene and the endocrine pathway involving the gonadal peptides, inhibin A and B, may be involved in the pathogenesis of osteoporosis in men. Further larger studies are needed for confirmation.
Keywords:
Bones,
Bone Research
Conference:
2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society, Cambridge, United Kingdom, 27 Jun - 29 Jun, 2011.
Presentation Type:
Poster
Topic:
Abstracts
Citation:
Sim
S,
Fogelman
I and
Hampson
G
(2011). A polymorphism in the inhibin alpha-subunit gene is associated with bone mineral density (BMD) and serum inhibin b (INH b) concentrations in men.
Front. Endocrinol.
Conference Abstract:
2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society.
doi: 10.3389/conf.fendo.2011.02.00061
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Received:
30 Sep 2011;
Published Online:
30 Sep 2011.
*
Correspondence:
Ms. S Sim, St Thomas' Hospital, Department of Clinical Chemistry, London, United Kingdom, selina.sim@kcl.ac.uk