Association of SNP (rs1042579) in thrombomodulin gene and plasma thrombomodulin level in North Indian children with Kawasaki disease

Background Kawasaki disease (KD) is the commonest systemic vasculitis in children. It predisposes to development of coronary artery abnormalities (CAAs). Thrombomodulin (THBD) gene polymorphism rs1042579 is associated with high risk of cerebrovascular diseases. However, association of THBD polymorphism (rs1042579) and plasma thrombomodulin (TM) levels with susceptibility to KD and CAAs remains unclear. Methods and results Polymorphism in THBD gene (rs1042579) was analysed in 50 KD patients and 50 age, gender and ethnicity matched controls using Sanger sequencing. Plasma TM levels were measured by ELISA. Results Mean plasma TM level (+/- SD) in KD patients was 2549.41 (+/- 853.18) pg/ml and in controls was 2298.03 (+/- 869.14) pg/ml; p = 0.042. Mean plasma TM levels in CC genotype was 2299.98 (+/- 834.88) pg/ml and in CT/TT genotype was 2837.96 (+/- 857.14) pg/ml; p = 0.005. Genotyping data did not reveal significant differences in patients with KD as compared to controls (p = 0.25), and in KD patients with and without CAAs (p = 0.407). Odds of finding T allele in cases were 2.07 times greater than in controls (p = 0.093). Conclusions This is the first study from India, and second in the world, that investigates association of THBD gene polymorphism with KD. This is also the first study to assess plasma TM levels in KD patients. Our data show that plasma TM levels were significantly higher in KD patients with CT/TT genotypes. Further, the polymorphism rs1042579 at exon 1 of THBD gene was found to be more common in KD patients than in controls although the difference was not statistically significant.

Automated summary

This study is the first investigation from India and the second in the world that explores the association between THBD gene polymorphism and Kawasaki disease. It's also the first study to assess plasma thrombomodulin levels in Kawasaki disease patients. The results showed that Kawasaki disease patients with CT/TT genotypes had significantly higher plasma thrombomodulin levels.