Angiogenesis related genes in Takayasu Arteritis (TAK):  robust association with Tag SNPs of IL-18 and FGF-2 in a South Asian Cohort

AbstractWe performed genetic association study for genes encoding angiogenic and angiostatic proteins in patients with Takayasu arteritis (TAK). A total of 96 SNPs involving 60 genes were studied. Genotyping was performed in Fluidigm 96.96 Dynamic Array chip. All statistical analysis for SNP evaluation was performed using PLINK software. Initial analyses revealed five SNPs from three genes [IL-18 (encodes Interleukin-18),FGF2 (encodes Fibroblast Growth Factor-2), andANGPT1 (encodes Angiopoietin-1)] as significantly different between controls and cases (uncorrectedp <  0.05). After permutation-based analysis, two tag SNPs on the promoter region ofIL-18 (rs187238 and rs1946518) and one 3 ’UTR tag SNP (rs1476217) ofFGF2 were significantly associated with susceptibility to TAK, with p and OR (95% CI) of 0.0006 and 1.64 (1.25 –2.17), 0.03 and 1.28 (1.02–1.64)& 0.016 and 1.33 (1.05 –1.67), respectively; while, the two tag SNPs ofANGPT1 gene (rs6469101 and rs16875900) showed a trend (p = 0.055&p = 0.051, respectively after permutation based correction). There is robust linkage disequilibrium between the two tag SNPs ofIL-18 gene as validated by 1000 genome data of South Asian population; the eQTL effects of these tag SNPs ofIL-18 andFGF2 genes on adjacent genes further suggest that these tag SNPs act as genetic risks for development of TAK in South Asians, with possible functional implications towards future biomarker development. Genotype phenotype st...

Source: Journal of Human Genetics - October 17, 2023 Category: Genetics & Stem Cells Source Type: research