Length of FMR1 repeat alleles within the normal range does not substantially affect the risk of early menopause.

Study Question: Is the length of FMR1 repeat alleles within the normal range associated with the risk of early menopause?

Summary Answer: The length of repeat alleles within the normal range does not substantially affect risk of early menopause.

What Is Known Already: There is a strong, well-established relationship between length of premutation FMR1 alleles and age at menopause, suggesting that this relationship could continue into the normal range. Within the normal range, there is conflicting evidence; differences in ovarian reserve have been identified with FMR1 repeat allele length, but a recent population-based study did not find any association with age at menopause as a quantitative trait.

Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency.

Purpose: Primary ovarian insufficiency before the age of 40 years affects 1% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR1 expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for primary ovarian insufficiency, but these are likely to be biased as compared with cases in the general population.

Common genetic variants are significant risk factors for early menopause: results from the Breakthrough Generations Study.

Women become infertile approximately 10 years before menopause, and as more women delay childbirth into their 30s, the number of women who experience infertility is likely to increase. Tests that predict the timing of menopause would allow women to make informed reproductive decisions. Current predictors are only effective just prior to menopause, and there are no long-range indicators.

CCAAT/enhancer binding protein alpha, beta and delta gene variants: associations with obesity related phenotypes in the Leeds Family Study.

Objective: To identify novel polymorphisms in the genes encoding the transcription factors CCAAT/enhancer binding protein alpha, beta and delta ( CEBPA, CEBPB, CEBPD) and investigate associations between polymorphisms and obesity-related phenotypes.

Methods: Denaturing high-performance liquid chromatography (HPLC) was used to screen for novel gene variants and polymorphisms were genotyped in stored DNA from participants of the Leeds Family Study (537 subjects from 89 families). Genotype and haplotype analyses were carried out in STATA and PBAT, respectively.

Intermediate sized CGG repeats are not a common cause of idiopathic premature ovarian failure.

Background: It is recognized that FMR1 premutation expansions are associated with premature ovarian failure (POF), but the role of smaller repeats at the boundary of premutation and normal is less clear.

Methods: We have therefore investigated the incidence of these intermediate sized FMR1 CGG repeats (35-58 repeats) in a series of 366 women ascertained because of menopause before the age of 40.

Results: We found no significant difference in the incidence of intermediates in cases compared with controls.

Genetic variation at the interleukin-1 locus is a determinant of changes in soluble endothelial factors in patients with acute coronary syndromes.

Acute coronary syndromes (ACSs) are associated with both systemic inflammatory activation and endothelial cell activation, and both of these are linked to patient outcome. Genetic variation at the interleukin-1 (IL-1) locus influences the clinical patterns of inflammatory disease. We therefore examined the association between IL-1 gene polymorphisms and levels of systemic inflammatory activation markers [C-reactive protein (CRP) and IL-1 receptor antagonist (IL-1ra)] and of soluble endothelial activation markers [von Willebrand factor (vWF) and E-selectin], in a cohort of 63 patients presenting with non-ST-elevation ACS.