Correlations of AFAP1, GMDS and PTGFR gene polymorphisms with intra-ocular pressure response to latanoprost in patients with primary open-angle glaucoma

J Clin Pharm Ther. 2017 Feb;42(1):87-92. doi: 10.1111/jcpt.12468. Epub 2016 Nov 12.

Abstract

What is known and objective: Genomewide association studies have identified a number of genetic variants that are associated with the development of primary open-angle glaucoma (POAG). This study aimed to explore possible correlations of common single nucleotide polymorphisms (SNPs) in AFAP1, GMDS and PTGFR genes with intra-ocular pressure (IOP) response to latanoprost in POAG patients.

Methods: From January 2012 to December 2014, 135 patients with POAG were enrolled into our study. Direct sequencing of polymerase chain reaction (PCR) products was used to analyse the distribution of allelic and genotypic frequencies of AFAP1 rs11723068 G>A and rs757253 T>C, GMDS rs9503012 C>T and rs17134549 T>A, and PTGFR rs3753380 C>T and rs3766355 A>C.

Results and discussion: After 1, 2 and 4 weeks of latanoprost treatment, the IOP of POAG patients decreased significantly (all P < 0·05). The genotype frequencies of six SNPs in AFAP1, GMDS and PTGFR genes were conformed to Hardy-Weinberg equilibrium (HWE). Before latanoprost treatment, the baseline IOP levels of POAG patients carrying CC+AC genotypes of PTGFR rs3766355 A>C were higher than those carrying AA genotype (P < 0·05). After 1, 2 and 4 weeks of latanoprost treatment, POAG patients carrying TT genotype of GMDS rs9503012 C>T showed better response to latanoprost than those carrying CC+CT genotype (P < 0·05). Similarly, POAG patients carrying AA genotype of PTGFR rs3766355 A>C showed better response to latanoprost than those carrying CC+AC genotypes (P < 0·05). Logistic regression analysis showed that age, CC+CT genotypes of GMDS rs9503012 C>T and CC+AC genotypes of PTGFR rs3766355 A>C were independent risk factors for poor response to latanoprost in POAG patients.

What is new and conclusions: GMDS rs9503012 C>T and PTGFR rs3766355 A>C may be associated with IOP response to latanoprost in POAG patients.

Keywords: GMDS; PTGFR; AFAP1; intra-ocular pressure; latanoprost; polymorphism; primary open-angle glaucoma.

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Female
  • Genotype
  • Glaucoma, Open-Angle / drug therapy*
  • Glaucoma, Open-Angle / genetics
  • Humans
  • Hydro-Lyases / genetics*
  • Intraocular Pressure / drug effects
  • Intraocular Pressure / genetics*
  • Latanoprost
  • Male
  • Microfilament Proteins / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / drug effects
  • Polymorphism, Single Nucleotide / genetics*
  • Prostaglandins F, Synthetic / therapeutic use*
  • Receptors, Prostaglandin / genetics*
  • Young Adult

Substances

  • AFAP1 protein, human
  • Antihypertensive Agents
  • Microfilament Proteins
  • Prostaglandins F, Synthetic
  • Receptors, Prostaglandin
  • prostaglandin F2alpha receptor
  • Latanoprost
  • Hydro-Lyases
  • GDPmannose 4,6-dehydratase