We 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), and ANGPT1 (encodes
Angiopoietin-1)] as significantly different between controls and cases (uncorrected p < 0.05). After permutation-based analysis, two tag SNPs on the promoter region of
IL-18 (rs187238 and rs1946518) and one
3'UTR tag SNP (rs1476217) of
FGF2 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 of ANGPT1 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 of
IL-18 gene as validated by 1000 genome data of South Asian population; the eQTL effects of these tag SNPs of
IL-18 and
FGF2 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 study by genetic model-based analysis also revealed associations between genotype subsets and clinical features like
fever, visual loss, left subclavian and coronary artery involvement in our TAK patients.