Thrombospondin 1 polymorphism associated with decreased expression and increased risk of pterygium

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 259; no. 8; pp. 2301 - 2307
• Main Authors: Simon, Lilla S., Keshav, Vinny, Baharozian, Connor, Masli, Sharmila, Lee, Hyunjoo J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2021; Springer Nature B.V
• Subjects: Alleles; Case-Control Studies; Deoxyribonucleic acid; DNA; Gene expression; Gene Frequency; Gene polymorphism; Genetic Predisposition to Disease; Genetics; Genotype; Genotype & phenotype; Genotyping; Humans; Medicine; Medicine & Public Health; Ophthalmology; Peripheral blood; Pilot Projects; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide; Pterygium - genetics; Single-nucleotide polymorphism; Thrombospondin; Thrombospondin 1 - genetics; Pterygium; Thrombospondin; rs1478604
• ISSN: 0721-832X; 1435-702X; 1435-702X
• DOI: 10.1007/s00417-021-05121-3

Purpose To assess the potential association of a thrombospondin 1 gene ( THBS1 ) single-nucleotide polymorphism ( rs1478604 ) with thrombospondin 1 (TSP-1) mRNA expression, as well as the risk of pterygium, in a pilot study. Methods DNA and RNA were isolated from peripheral blood samples collected from normal volunteer subjects ( n = 39). In addition, DNA was isolated from conjunctival tissue samples collected during pterygium excision surgeries ( n = 42). Relative expression of TSP-1 mRNA was measured by quantitative RT-PCR, and rs1478604 genotype was determined using a TaqMan SNP genotyping assay. Genotype frequencies were compared with mRNA expression and between pterygium samples and normal controls. Results Expression of TSP-1 mRNA was significantly lower in the peripheral blood of normal subjects who were homozygous for the C allele of rs1478604 (CC) compared to TT and CT genotypes ( p = 0.004) . When we compared rs1478604 genotypes between normal and pterygium patients, we found that the CC genotype was also associated with an increased risk of pterygium compared to TT (odds ratio (OR) = 5.39, 95% CI [1.26–22.99], p = 0.028), CT (OR = 7.86, 95% CI [1.92–32.17], p = 0.003), and combined CT and TT genotypes (OR = 6.67; 95% CI = [1.75–25.37]; p = 0.003). Conclusions We found that the C allele of rs1478604 was associated with both lower TSP-1 expression and higher risk of pterygium, possibly implicating TSP-1 in the pathogenesis of pterygium.