Hemopexin levels not linked to AMD or genetic variants in patients with age-related macular degeneration

The study also failed to confirm the finding of a previous protein quantitative trait locus (pQTL) study that variants at the CFH locus were associated with hemopexin levels.

A previous pQTL analysis revealed a strong association between hemopexin levels and genetic variants at the complement factor H locus. In the recent analysis of hemopexin (HPX) levels, Susette Lauwen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands, and colleagues aimed to determine HPX plasma levels in patients with AMD and compared them with those in controls. They also investigated if genetic variants at the CFH locus are associated with HPX plasma levels.

For this purpose, the researchers quantified HPX levels in 200 advanced AMD cases and 200 controls using ELISA (enzyme-linked immunosorbent assay) and compared them between the two groups. Also, HPX levels were analyzed per genotype group of three HPX-associated variants (rs10801582, rs10494745, and rs61818956) and four AMD-associated variants (rs61818924 [proxy for rs61818925], rs10922109, rs570618, and rs794362 [proxy for rs187328863]) at the CFH locus. The team found no significant differences in HPX levels between the genotype groups.

The study revealed the following findings:

· HPX levels were similar in the control group compared with the AMD group.

· The three variants at the CFH locus, previously associated with the HPX levels, showed no association with the HPX levels in the data set.

· No significant differences in HPX levels were detected between the different genotype groups of AMD-associated variants at the CFH locus.

· The authors found associations between HPX levels and sex, BMI, and smoking. However, in a multivariate analysis correcting for age, sex, BMI, and smoking, investigators found no significant differences in HPX levels between the AMD and control groups.

The research team indicated an interest in analyzing causation in future analyses, noting only associations between HPX levels and variants in the CFH locus and between HPX and FHR4 levels are known.

“Furthermore, based on this study, we cannot exclude the possibility that HPX protein levels might be differently regulated locally in AMD patients compared with controls, which might not be reflected in the blood,” investigators wrote.

Reference:

Lauwen S, Bakker B, de Jong EK, Fauser S, Hoyng CB, Lefeber DJ, den Hollander AI. Analysis of hemopexin plasma levels in patients with age-related macular degeneration. Mol Vis. 2022 Dec 31;28:536-543. PMID: 37089696; PMCID: PMC10115365.