Association of ARMS2, HTRA1 and CFH genes polymorphisms in patients with age-related macular degeneration in the Malaysian population

• Published in: Egyptian Journal of Medical Human Genetics Vol. 25; no. 1; pp. 79 - 11
• Main Authors: Ismail, Fazliana, Junit, Sarni Mat, Chin, Lee Ching, Jayapalan, Jaime Jacqueline, Subrayan, Visvaraja
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2024; Springer; Springer Nature B.V; SpringerOpen
• Subjects: Age; Age-related macular degeneration; Alleles; Amino acids; Analysis; ARMS2 gene; Care and treatment; CFH gene; Chromosomes; DNA sequencing; Eye diseases; Gene amplification; Gene frequency; Genealogy; Genes; Genetic aspects; Genetic diversity; Genetic factors; Genetic polymorphisms; Genotyping; Health aspects; Health care access; HTRA1 gene; Leukocytes (mononuclear); Macular degeneration; Medicine; Medicine & Public Health; Nucleotide sequencing; Peripheral blood mononuclear cells; Polymorphism; Population; Population genetics; Population studies; Proteins; Quality of life; Sequence analysis; Single nucleotide polymorphism; Visual acuity; White people; China; Malaysia; United States > US; Germany; Age-related macular degeneration; gene; Single nucleotide polymorphism
• ISSN: 1110-8630; 2090-2441
• DOI: 10.1186/s43042-024-00549-8

Background Despite extensive research efforts, understanding the precise causes and molecular underpinnings of age-related macular degeneration (AMD) remains elusive. Exploring different populations becomes crucial to establish conclusive insights into the role of genetic factors in AMD. Methodology This study aimed to investigate the association between the well-documented major risk alleles in the HTRA1, ARMS2 and CFH genes with AMD in the Malaysian multi-ethnic population. A total of 205 subjects were enrolled in this study, 103 were diagnosed with AMD while 102 represented the control subjects. Genomic DNA was extracted from peripheral blood mononuclear cells and gene amplification was performed by polymerase chain reaction. Subsequently, genotyping for the HTRA1 , ARMS2 and CFH genes was performed using direct DNA sequencing analysis. Results Significant associations ( p  < 0.05) were detected with AMD for both SNP rs11200638: G > A in the promoter of HTRA1 and rs10490924: G > T in ARMS2 but not for variant Y402H in CFH gene ( p  > 0.05) in our study population. The A allele frequency of rs11200638 in the HTRA1 promoter was 51.9% in cases versus 39.2% in controls ( p  = 0.010). The frequency of AA genotype was 28.2% for AMD cases, compared to 17.6% in controls (OR 2.58, 95% CI 1.19–5.58; p  = 0.043). The frequency of the TT genotype of rs10490924 in ARMS2 was 25.2% in cases versus 8.8% in controls (OR 2.23, 95% CI 0.83–5.99; p  = 0.002). Conclusion The study reveals an association between specific genetic variants in the HTRA1 and ARMS2 genes and the occurrence of AMD in the Malaysian population. However, contrary to expectations, the study did not identify a substantial correlation between AMD and the Y402H variant of the CFH gene in this specific population.