Toll-Like Receptor 3 Polymorphism rs3775291 Is Not Associated with Choroidal Neovascularization or Polypoidal Choroidal Vasculopathy in Chinese Subjects

Abstract

Background/Aims: Age-related macular degeneration (AMD) is a leading cause of visual impairment. A single-nucleotide polymorphism (SNP; rs3775291) in the Toll-like receptor 3 (TLR3) gene has recently been implicated in the pathogenesis of AMD in Caucasian populations. The aim of this study was to examine this association in Chinese persons with choroidal neovascularization (CNV) secondary to AMD and polypoidal choroidal vasculopathy (PCV). Methods: This was an observational cross-sectional study in Singapore. Study subjects were of Chinese ethnicity and included patients with exudative maculopathy and normal control subjects. The diagnoses of CNV and PCV were made based on fundus examination, fluorescein angiography and indocyanine green angiography findings. Genomic DNA was extracted, and genotypes were determined by bidirectional DNA sequencing. We compared the allele and genotype frequencies between subjects with CNV and PCV with controls using the software PLINK. Results: A total of 246 subjects with exudative maculopathy (consisting of 126 with CNV and 120 with PCV) and 274 normal control subjects were recruited. The distribution of rs3775291 SNP genotypes for CNV and PCV was not significantly different from that for normal controls. Conclusion: This study indicates that the TLR3 rs3775291 gene polymorphism is not associated with CNV and PCV in Singaporean Chinese patients.

Toll-like receptor 3 polymorphism is not associated with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in the Chinese

“…In our age-and gender-adjusted analysis, we provide new data that the TLR3 gene variant is not associated with either nAMD or PCV in Chinese. This is consistent with Sng et al (2011) and Zhou et al (2011), who proposed that the TLR3 mutation reduces binding capacity to dsRNA, protecting against GA rather than the neovascular phenotype. Moreover, genes that have been implicated in the pathogenesis of nAMD and PCV are usually factors likely involved in ischemia, inflammation, and local synthesis and secretion of angiogenic factors (Swaroop et al, 2007;Veritti et al, 2012).…”

“…This could have led to a fallacious association because AMD is strongly age-related. Other studies with primarily Caucasian subjects, adjusted for age and gender, did not detect an association between the rs3775291 SNP and either GA or neovascular AMD (Edwards et al, 2008;Allikmets et al, 2009;Cho et al, 2009b) Furthermore, Sng et al (2011) found that the TLR3 polymorphism rs3775291 was not associated with nAMD or PCV in Chinese. Thus, it remains uncertain if TLR3 is associated with nAMD or PCV.…”

Genetic risk, ethnic variations and pharmacogenetic biomarkers in AMD and polypoidal choroidal vasculopathy

“…Genes in the collagen matrix pathway, COL10A1 and COL8A1 [24], the extracellular matrix pathway, TIMP3 [24,37], the angiogenesis pathway, VEGF [3,24], also show association with AMD. Other genes, such as those involved with inflammation and immunity, TLR3 [61] and SOD2 [62], and the 9p21 region [63] did not show an association with AMD. In recent years, meta-analyses demonstrated that the REST-C4orf14-POLR2B-IGFBP7 at 4q21 does not show an association with AMD, while the T allele at rs13278062 of TNFRSF10A-LOC389641 at 8p21 decreases risk of AMD [26,64] ( Table 1 ).…”

“…Due to a strong linkage disequilibrium across this region, it is difficult to genetically distinguish between these two susceptible candidates and prioritize of their importance toward disease pathogenesis [99]. Other studies have also examined the association of C2/CFB [90,92,96,100], SERPING1 [101,102], ELN [103-105], PEDF [106-108], APOE [59], SOD2 [62], TLR3 [61], the 9p21 region [63], RDBP [100], SKIV2L [100], and C3 [98] with PCV in different ethnicities, but meta-analysis shows that the results of these associations are inconclusive and sometimes underpowered [94]. A recent study demonstrated that REST-C4orf14-POLR2B-IGFBP7 at 4q21 did not show an association with PCV; however, the T allele at rs13278062 of TNFRSF10ALOC389641 at 8p21 decreases risk of PCV.…”

Genetics of Immunological and Inflammatory Components in Age-related Macular Degeneration

“…64 Another study focusing on a separate group of Singaporean Chinese indicated that the TLR3 rs3775291 is not associated with CNV and polypoidal choridal vasculopathy (PCV), a condition similar to but distinct from AMD. 65 …”