Effects of TIMP-2 Polymorphisms on Retinopathy of Prematurity Risk, Severity, Recurrence, and Treatment Response

Int J Mol Sci. 2022 Nov 17;23(22):14199. doi: 10.3390/ijms232214199.


Tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in endogenous angiogenesis besides the regulation of matrix metalloproteinase (MMP) activity. Associations between TIMP-2 gene polymorphisms and the risk of retinopathy of prematurity (ROP) were examined. Premature infants born between 2009 and 2018 were included. Five single-nucleotide polymorphisms (SNPs) of TIMP-2 were analyzed with real-time polymerase chain reaction (PCR). Multivariate logistic regression was applied to model associations between TIMP-2 polymorphisms and ROP susceptibility and severity. The GA+AA genotype in individuals with the TIMP-2 polymorphism of rs12600817 was associated with a higher risk of ROP (odds ratio [OR]: 1.518, 95% confidence interval [CI]: 1.028-2.242) compared with their wild-type genotypes. The AA genotype (OR: 1.962, 95% CI: 1.023-3.762) and the AA+GA genotype (OR: 1.686, 95% CI: 1.030-2.762) in individuals with the rs12600817 polymorphism had higher risks of severe, treatment-requiring ROP relative to their wild-type counterparts. In patients with treatment-requiring ROP, the AG+GG genotypes in the TIMP-2 polymorphism of rs2889529 were correlated with the treatment response (p = 0.035). The TIMP-2 polymorphism of rs12600817 help in predicting ROP risks in preterm infants, while the polymorphism of rs2889529 can serve as a genetic marker in evaluating the ROP treatment response.

Keywords: TIMP-2; retinopathy of prematurity; single nucleotide polymorphisms (SNPs).

MeSH terms

  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Polymorphism, Single Nucleotide
  • Retinopathy of Prematurity* / genetics
  • Retinopathy of Prematurity* / therapy
  • Tissue Inhibitor of Metalloproteinase-2* / genetics


  • Tissue Inhibitor of Metalloproteinase-2