HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Epistasis between polymorphisms in ACVR2B and ADAMTS19 is associated with premature ovarian failure.

AbstractOBJECTIVE:
This study investigated whether epistasis between single nucleotide polymorphisms (SNPs) within ACVR2B (activin A receptor, type IIB) and ADAMTS19 (ADAM metallopeptidase with thrombospondin type 1 motif, 19) genes is associated with premature ovarian failure (POF).
METHODS:
One hundred twenty women with POF and 152 controls were recruited for stage I, and 1,641 additional female controls participated in stage II. GoldenGate assay with VeraCode technology was used for genotyping ACVR2B and ADAMTS19 SNPs in stage I. In stage II, we obtained genotype data for SNPs using Affymetrix Genome-Wide Human SNP array 5.0 and imputed data using IMPUTE program from the Korean Genome Epidemiology Study.
RESULTS:
In stage I, five combinations showed significant synergistic interactions after Bonferroni correction. One SNP (rs1468077 within 5' flanking region) and two intronic SNPs (rs2268753 and rs2268757) in ACVR2B and three intronic SNPs within ADAMTS19 (rs13158524, rs1476083, and rs1972624) were involved in synergistic interactions in a recessive manner. In stage II and combined analyses, we could not find any significant interactions between the SNPs. However, diplotypes within ACVR2B and ADAMTS19 that consist of risk genotypes or alleles in the results of significant synergistic interactions between SNPs showed significant interactions after Bonferroni correction. Thirteen and nine significant synergistic interactions were found in a dominant model in stage II and combined analyses, respectively (strongest association in combined analysis: odds ratio, 5.93; 95% CI, 2.47-14.20; P = 6.65 × 10(-5)).
CONCLUSIONS:
Epistasis between polymorphisms within ACVR2B and ADAMTS19 is significantly associated with susceptibility to POF.
AuthorsJung-A Pyun, Sunshin Kim, KyuBum Kwack
JournalMenopause (New York, N.Y.) (Menopause) Vol. 22 Issue 2 Pg. 212-6 (Feb 2015) ISSN: 1530-0374 [Electronic] United States
PMID25051287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • ACVR2B protein, human
  • Activin Receptors, Type II
  • ADAM Proteins
  • ADAMTS Proteins
  • ADAMTS19 protein, human
Topics
  • ADAM Proteins (genetics)
  • ADAMTS Proteins
  • Activin Receptors, Type II (genetics)
  • Asian People (genetics)
  • Epistasis, Genetic
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Primary Ovarian Insufficiency (genetics)
  • Seoul

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: