Author/Editor | Harris, Sarah E; Chand, Ashwini L; Winship, Ingrid M; Geršak, Ksenija; Nishi, Yoshihiro; Yanase, Toshihiko; Nawata, Hajime; Shelling, Andrew N | |
Title | INHA promoter polymorphisms are associated with premature ovarian failure | |
Type | članek | |
Source | Mol Hum Reprod | |
Vol. and No. | Letnik 11, št. 11 | |
Publication year | 2005 | |
Volume | str. 779-84 | |
Language | eng | |
Abstract | Inhibin is an important glycoprotein that is involved in folliculogenesis. INHA, the gene encoding the inhibin alpha subunit, was recently proposed as a candidate for premature ovarian failure (POF), a syndrome that leads to the cessation of ovarian function under the age of 40 years. 70 POF patients and 70 controls were screened for the previously identified INHA -16C>T transition mutation. The T allele was found in 31/70 (44.3%) of controls, but only 18/70 (25.7%) of POF patients. This result indicates that the T allele is significantly underrepresented in the POF patient population (Fisher's exact test, two-tail: P = 0.033). Sequence analysis of the INHA promoter in 50 POF patients and 50 controls identified a highly polymorphic imperfect TG repeat at approximately -300 bp, that consisted of four common haplotypes (A, B, C and D). The -16T allele is linked to the shortest repeat haplotype (haplotype C). Despite the association between haplotype C and POF, no significant difference was found between the promoter activity of a luciferase reporter construct containing haplotype C, and most of the other haplotypes tested. Interestingly, haplotype B failed to show any promoter activity. We conclude that the inheritance of specific INHA promoter haplotypes predispose to the development of premature ovarian failure. | |
Descriptors | OVARIAN FAILURE, PREMATURE INHIBIN PROMOTER REGIONS (GENETICS) ADULT BASE SEQUENCE GENOTYPE HAPLOTYPES AUSTRALIA REFERENCE VALUES REPETITIVE SEQUENCES, NUCLEIC ACID SLOVENIA |