Genetic factors associated with age-related macular degeneration modulating plasma inflammatory biomarker levels in patients with AIDS

Ophthalmic Genet. 2024 Aug;45(4):337-342. doi: 10.1080/13816810.2024.2330380. Epub 2024 Mar 25.

Abstract

Introduction: Patients with the acquired immunodeficiency syndrome (AIDS) have an increased prevalence and incidence of intermediate-stage age-related macular degeneration (AMD). Several elevated plasma inflammatory biomarkers are associated with increased incidence of intermediate-stage AMD in this population. We evaluated the association between AMD risk alleles and plasma inflammatory biomarker levels in persons with AIDS.

Materials and methods: Cryopreserved plasma specimens of 229 non-Hispanic White and 252 non-Hispanic blacks from the Longitudinal Study of the Ocular Complications of AIDS cohort were assayed for plasma levels of soluble tumor necrosis factor receptor (sTNFR) 2, interleukin (IL)-18, C × 3motif chemokine ligand 1 (CX3CL1), C-reactive protein (CRP), and soluble CD14 (sCD14). Genotyping included AMD-associated variants rs10801553 and rs800292 for complement factor H (CFH) rs9332739 and rs547154 for complement factor 2 (C2), rs2230199 for C3, rs2285714 for CFI, and rs3732379 and rs3732378 for C × 3motif chemokine receptor 1 (CX3CR1).

Results: In Whites, AMD low-risk CX3CR1 variants (V249I and T280M) were associated with reduced plasma levels of IL-18. In Blacks, AMD low-risk C3 R102G and low-risk CX3CR1 T280M variants were associated with reduced CRP levels.

Conclusions: Genetic variants in AMD-associated immune genes may influence AMD-associated systemic plasma inflammatory biomarker levels in patients with AIDS.

Keywords: Acquired immunodeficiency syndrome; age-related macular degeneration; genetic risk factors; inflammatory biomarkers.

MeSH terms

  • Acquired Immunodeficiency Syndrome* / blood
  • Acquired Immunodeficiency Syndrome* / genetics
  • Biomarkers* / blood
  • Black or African American / genetics
  • C-Reactive Protein / analysis
  • C-Reactive Protein / genetics
  • C-Reactive Protein / metabolism
  • CX3C Chemokine Receptor 1 / genetics
  • Chemokine CX3CL1* / blood
  • Chemokine CX3CL1* / genetics
  • Complement Factor H / genetics
  • Female
  • Genotype
  • Humans
  • Interleukin-18 / blood
  • Interleukin-18 / genetics
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharide Receptors / genetics
  • Macular Degeneration* / blood
  • Macular Degeneration* / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptors, Tumor Necrosis Factor, Type II / blood
  • Receptors, Tumor Necrosis Factor, Type II / genetics
  • Risk Factors
  • White / genetics

Substances

  • Biomarkers
  • C-Reactive Protein
  • Chemokine CX3CL1
  • Complement Factor H
  • CX3C Chemokine Receptor 1
  • CX3CL1 protein, human
  • CX3CR1 protein, human
  • Interleukin-18
  • Lipopolysaccharide Receptors
  • Receptors, Tumor Necrosis Factor, Type II