ClinVar

This variant is classified as a variant of unknown significance because there is conflicting evidence regarding its contribution to premature ovarian failure (POF; see 311360).

In 50 New Zealand patients with premature ovarian failure and 20 from Slovenia, Harris et al. (2005) screened for a -16C-T polymorphism in the promoter region of the INHA gene and observed underrepresentation of the T allele in POF patients compared to controls. Analysis of the INHA promoter region revealed that the imperfect TG repeat element was highly polymorphic, and that the shortest repeat (designated haplotype C) was in linkage disequilibrium with -16T. However, no significant differences in promoter activity were observed between haplotype C and 7 other promoter haplotypes, except for 1 (haplotype B) that showed no promoter activity.

In 61 Argentinian women with POF, 18 of whom had a known autoimmune disorder, and 82 controls, Sundblad et al. (2006) analyzed the INHA gene but could not demonstrate an association between the -16C-T variant and the risk of POF. In addition, studying 46 women below the age of 40 with regular menses, the authors found no significant differences in inhibin A, inhibin B, or pro-alpha-C peptide levels between women who were homozygous for CC at -16 or women who carried CT or TT alleles. Sundblad et al. (2006) concluded that the -16C-T variant may not be associated with POF disease.

In 3 independent POF cohorts, consisting of a total of 611 patients and 1,084 matched controls from Italy and Germany, Corre et al. (2009) found no association between the -16C-T variant and POF.