How polymorphic markers contribute to genetic diseases in different populations? The study of inhibin A for premature ovarian insufficiency

Abstract

Objective To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls.Methods A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software.Results Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide.Conclusion There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.

Association of polymorphism c.‐124G>A and c.‐16 C>T in the promoter region of human INHA gene with altered sperm parameters; A pilot study

“…Controls (Normal Sperm Parameters): Subjects who had the following sperm parameters were included in “Normal Sperm Parameters” 22 (Table 1).…”

“…It is postulated that mutations in the inhibin genes lead to a reduction in circulating inhibins. This results in an increase in FSH levels causing alterations in follicle recruitment and premature depletion of the follicle pool, ultimately causing disturbances in the process of spermatogenesis 11‐15,21‐23 …”

The impact of INH-alpha (rs12720062 G/A) gene polymorphism and serum vitamin D level on risk of premature ovarian failure

“…Indeed, it is suggested that the low level of inhibin is part of the pathogenesis of the disease because it will lead to increased activity of activin hormone that will stimulate FSH and leads to increased rate of folliculogenesis and premature exhaustion of ovarian follicles and thereby early menopause (Chand et al, 2010;Christofolini et al, 2017). The low serum level of inhibin-alpha has been linked to genetic variations in the genes that encode inhibin and the suggestion that such genetic variation will cause reduction in the production and secretion of this hormone with resulted augmented activin hormone effect (Christofolini et al, 2017).…”

“…Previuos studies, including those by Chapman et al (2015) and Mutlu and Erdem (2012), which found that the INH1 G769A mutation was present in 10.5% of cases with sporadic POF as opposed to 0.005% of controls. A sample of 97 fertile controls and 70 women with early ovarian insufficiency were compared in a Brazilian study by Christofolini et al (2017). The G769A variation manifests to be uncommon in Brazilian women having premature ovarian failure since it was only discovered in one woman in the Premature Ovarian failure category and in no controls.…”