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Association of rs12997 variant in the ACVR1 gene: a member of bone morphogenic protein signaling pathway with primary open-angle glaucoma in a Saudi cohort
  1. Altaf A Kondkar1,2,3,
  2. Taif A Azad1,
  3. Tahira Sultan1,
  4. Essam A Osman1,
  5. Faisal A Almobarak1,2,
  6. Saleh A Al-Obeidan1,2
  1. 1Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  2. 2Glaucoma Research Chair in Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  3. 3King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
  1. Correspondence to Dr Altaf A Kondkar, Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; akondkar{at}


We investigated the association between variants rs12997 in activin A receptor type I (ACVR1) and rs1043784 in BMP6 located in the 3' untranslated region, and primary open-angle glaucoma (POAG). The retrospective case-control study used TaqMan real-time PCR assay to genotype 400 subjects, including 150 patients with POAG and 250 controls. The minor ‘G’ allele of rs12997 in ACVR1 showed significant association with POAG (p=0.027, OR=1.39, 95% CI=1.03 to 1.87). Likewise, rs12997 genotypes showed moderate association with POAG in recessive (p=0.048, OR=1.80, 95% CI=1.01 to 3.20) and log-additive models (p=0.030, OR=1.39, 95% CI=1.03 to 1.87), but did not survive Bonferroni correction. Rs1043784 in BMP6 showed no associations. Furthermore, rs12997 G/G genotype significantly (p=0.033) increased the risk of POAG (twofolds) independent of age, sex and rs1043784 genotypes in regression analysis. However, clinical variables such as intraocular pressure and cup/disc ratio showed no association with both the polymorphisms. To conclude, the study shows a modest association between rs12997 in the ACVR1 gene, a member of the bone morphogenic protein signaling pathway and POAG. However, the results need further replication in large population-based cohorts and different ethnicities to validate its role as an important genetic biomarker.

  • activins
  • polymorphism
  • genetic
  • real-time polymerase chain reaction
  • translational medical research

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  • Contributors AAK: concept, experimental design, analysis, data interpretations, wrote and edited the manuscript. TAA, TS: sample preparation, genotyping and data acquisition, manuscript editing and revision. EAO, FAA: concept, recruitment, clinical diagnosis, data interpretation, manuscript editing and revision. SAA-O: concept, experimental design, recruitment, clinical diagnosis, data interpretation, manuscript editing and revision. All authors read and approved the final manuscript.

  • Funding This work was supported by King Saud University through Vice Deanship of Scientific Research Chair and Glaucoma Research Chair in Ophthalmology (#08–657).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study adhered to the Declaration of Helsinki principles and was approved by the institutional review board committee at the College of Medicine, King Saud University, Riyadh, Saudi Arabia. All the participants signed informed consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.