Association of BMP15 and GDF9 variants to premature ovarian insufficiency



To identify genetic variation associated to premature ovarian insufficiency (POI).


A total of 74 women with POI (group POI), 45 women with increased FSH levels (group high FSH), and 88 controls (non-POI) were studied. Genotyping of BMP15:c.-9C>G (rs3810682), BMP15:c.328+905A>G (rs3897937), and BMP15:c.852C>T (rs17003221); and GDF9:c.134-694G>A (rs4705974), GDF9:c.-31-951G>A (rs11748063), GDF9:c.-152G>C (rs30177), and GDF9:g.1073C>T (rs803224) was performed by the TaqMan methodology. Chi-square and Fisher’s exact tests were performed to evaluate the distribution of genotypes, alleles, odds ratio, and the Hardy-Weinberg equilibrium of each variation. Haplotype analysis was performed for each gene considering the case and control groups. Bonferroni’s correction was applied to chi-square and Fisher’s exact test data, and p values < 0.007 for genotypes and alleles and < 0.006 for haplotypes were considered significant.


It was observed a statistically significant difference in genotype distribution of BMP15:c.852C>T between group POI and controls (p < 0.001). TT and TC genotypes were more frequently observed in group POI. Genotype distribution in case group POI, however, was not in the Hardy-Weinberg equilibrium, due to the increased number of heterozygotes in the sample. Concerning GDF9, no association was found among the studied genetic variants and POI or high FSH groups.


It is concluded from the present study that the genotypes CT and TT from BMP15:c.852C>T variation may be risk factors for the development of POI.

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Correspondence to Denise Maria Christofolini.

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Santos, M., Cordts, E.B., Peluso, C. et al. Association of BMP15 and GDF9 variants to premature ovarian insufficiency. J Assist Reprod Genet 36, 2163–2169 (2019).

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  • Premature ovarian insufficiency
  • BMP15
  • GDF9
  • Infertility
  • Gene variants