Investigating the association between inhibin alpha gene promoter polymorphisms and premature ovarian failure
Received 26 June 2007; received in revised form 5 November 2007; accepted 5 November 2007. published online 13 February 2008.
Objective
To determine whether variants in the promoter region of the inhibin alpha gene (INHA) are associated with premature ovarian failure (POF).
Design
Mutational analysis of the INHA gene promoter in women with POF.
Setting
Academic institution.
Patient(s)
Patients with POF (n = 194) and controls (n = 162) from New Zealand and Slovenia.
Intervention(s)
Peripheral blood samples were screened for known polymorphisms in the INHA promoter (c.−16C→T, c.–124A→G, and an imperfect TG repeat at approximately −300 base pairs). Genotyping was performed by restriction fragment length polymorphism, forced restriction fragment length polymorphism, and nondenaturing high-performance liquid chromatography analysis.
Main Outcome Measure(s)
Genotypic status of INHA promoter polymorphisms.
Result(s)
Significant differences in INHA promoter allele frequencies were observed between POF patient populations and controls. Significant reductions in allele frequency were observed for the −16T allele (New Zealand POF) and −124G allele (total POF) and for INHA promoter haplotypes C (New Zealand POF) and D (Slovenian POF).
Conclusion(s)
We conclude that INHA promoter variants are associated with the development of POF.
aDiscipline of Oncology, University of Auckland, Auckland, New Zealand
bDepartment of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
cDepartment of Psychology, University of Edinburgh, Edinburgh, United Kingdom
dDepartment of Obstetrics and Gynaecology, University Medical Centre, Ljubljana, Slovenia
Reprint requests: Kathryn J. Woad, Ph.D., Discipline of Oncology, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand (FAX: 64-9-373-7927).
Supported by the University of Auckland Research Committee, Health Research Council of New Zealand, and Auckland Medical Research Foundation (all, Auckland, New Zealand).
ABSTRACT