Dizygotic twinning is not linked to variation at the alpha-inhibin locus on human chromosome 2

J Clin Endocrinol Metab. 2000 Sep;85(9):3391-5. doi: 10.1210/jcem.85.9.6831.


Natural multiple pregnancy in women leading to dizygotic (DZ) twins is familial and varies across racial groups, suggesting a genetic predisposition. Mothers of DZ twins have a higher incidence of spontaneous multiple ovulation and elevated FSH concentrations. FSH release is controlled by feedback of inhibin peptides from the ovary, and immunization against inhibin alpha-subunit results in an increased ovulation rate in animals. The inhibin alpha-subunit is therefore a candidate gene for mutations that may increase the frequency of DZ twinning. Restriction digests of a PCR product from exon 1 with the enzyme SpeI detects a C/T polymorphism at bp 128 with two alleles of 447 and 323/124 bp. The polymorphism was typed in 1,125 individuals from 326 pedigrees with 717 mothers of spontaneous DZ twins. The alpha-inhibin locus mapped within 3 centimorgans of D2S164, and linkage with DZ twinning was excluded [decimal log odds ratio (LOD) score, -2.81 at theta = 0]. There was complete exclusion of linkage (LOD, less than -2) of a gene conferring relative risk 1.8 (lambdas, >1.8) across the chromosome, except at the p-terminus region and a small peak (maximum LOD score, 0.6) in the region of D2S151-D2S326. Analysis using either recessive or dominant models excluded linkage with DZ twinning in this population (LOD score, less than -2.5) across chromosome 2. We conclude that dizygotic twinning is not linked to variation in the alpha-inhibin locus. The results also suggest that mutations in other candidates on chromosome 2, including the receptor for FSH and the betaB-inhibin subunit (INHBB) cannot be major contributors to risk for DZ twinning.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Chromosome Mapping
  • Chromosomes, Human, Pair 2 / genetics*
  • DNA / genetics
  • Exons / genetics
  • Female
  • Genetic Linkage / genetics*
  • Genome
  • Humans
  • Inhibins / genetics*
  • Pedigree
  • Polymorphism, Genetic / genetics
  • Pregnancy
  • Receptors, FSH / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Twins, Dizygotic / genetics*


  • Receptors, FSH
  • Inhibins
  • DNA