| Title: |
Functional polymorphisms in pigmentation-related genes MC1R and DCT display population-specific association with wet age-related macular degeneration |
| Authors: |
Reinisalo, Mika; Helisalmi, Seppo; Koskela, Ali; Küblbeck, Jenni; Liukkonen, Mikko; Mutikainen, Maija; Cree, Angela J.; Griffiths, Helen; Papp, Andras; Seitsonen, Sanna; Immonen, Ilkka; Soininen, Hilkka; Urtti, Arto; Hiltunen, Mikko; Winiarczyk, Mateusz; Resch, Miklos; Ratnayaka, J. Arjuna; Lotery, Andrew J.; Kaarniranta, Kai; Honkakoski, Paavo |
| Contributors: |
HUS Head and Neck Center; Silmäklinikka; Clinicum |
| Publisher Information: |
Elsevier B.V. |
| Publication Year: |
2026 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Dopachrome tautomerase; Melanocortin-1 receptor; Pigmentation; Polymorphism; Wet age-related macular degeneration; Otorhinolaryngology; ophthalmology |
| Description: |
Age-related macular degeneration (AMD) is among the leading causes of vision loss. Factors increasing the risk of AMD include aging, smoking, cardiovascular diseases and heritability. Although melanin pigment is known to protect retinal homeostasis, the link between pigmentation-related genes and AMD is unclear. We investigated associations between 26 variations in six pigmentation-related genes and wet AMD risk in a Finnish population, followed by replication in the United Kingdom (UK), Hungarian and Polish cohorts, totaling 775 patients and 959 controls. Associations of genetic components with smoking and body mass index (BMI) were tested in the Finnish and UK cohorts. The functionality of candidate variants in human retinal pigment epithelial (RPE) cells was evaluated using gene promoter analysis and gene silencing. Non-coding variants, rs1407995 in the dopachrome tautomerase ( DCT ) intron and rs3212351 in the melanocortin-1 receptor ( MC1R ) promoter, were associated with wet AMD in the Finnish cohort. The variant rs3212351 disrupts a binding site for transcription factor MITF and reduces MC1R expression in RPE cells. Unlike in the Finnish cohort, the data regarding the MC1R variant suggested a protective association in the Polish cohort. The incidence of AMD increased with age in all cohorts. Smoking increased AMD risk in the cohorts studied. Sex and BMI showed no associations. These findings suggest that variations in DCT and MC1R genes known to affect skin and eye pigmentation may also play a role in development of wet AMD. The observed population differences may be related to variable pigmentation traits. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
This research was funded by the Finnish Funding Agency for Technology and Innovation . Health Research Council of the Academy of Finland (grant numbers 296840 . 333302 , Gene Cell Nano Flagship). the Finnish Eye Foundation . the Kuopio University Hospital VTR grant (5503770). the Sigrid Juselius Foundation and the Päivikki and Sakari Sohlberg Foundation (all to Kai Kaarniranta) and by Health Research Council of the Academy of Finland (Paavo Honkakoski. grant number 40440). Academy of Finland , PROFI5 (Seppo Helisalmi, grant number 325 022). AJL was supported at the University of Southampton by funding from The Wellcome Trust (076169/A). American Health Assistance Foundation (M2007110). Macula Vision Research Foundation. TFC Frost Charitable Trust. Brian Mercer Charitable Trust. Macular Society. Hobart Trust and the Gift of Sight appeal.; https://hdl.handle.net/10138/628042; 105029348885; 001686890800001 |
| Availability: |
https://hdl.handle.net/10138/628042 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.89A79117 |
| Database: |
BASE |