157 - ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORPHISMS OF TGF-BETA PATHWAY IN NORTH INDIAN CHILDREN WITH KAWASAKI DISEASE: THE FIRST STUDY FROM THE INDIAN SUBCONTINENT

BACKGROUND:

KD is the most common vasculitis in children. The phenotype of KD in India appears to be different when compared to reports from the Western hemisphere as well as Japan. Although single nucleotide polymorphisms in the TGF-b pathway have been associated with development of KD, there are no studies from the Indian subcontinent. We aimed to study 7 single nucleotide polymorphisms (SNPs) of 4 genes of the TGF-b pathway putatively involved in the pathogenesis of KD: TGFB2: rs2796817; TGFBR2: rs1495592, rs795430; SMAD3: rs12901071, rs1438386, rs6494633; ADAM17: rs670540.

Methods:

 The study was conducted in a tertiary care hospital from July 2022-December 2023. Diagnosis of KD was based on standard criteria. We enrolled 47 patients with KD and 46 healthy controls. Genotypes for different SNPs genes of TGF-b pathway were compared between cases of KD and controls. Similarly, a comparison of the SNPs was made between KD patients with and without  CAAs by KASP assay.

Results:

Our results indicated that SNP rs1438386 of the SMAD3 gene exhibited higher odds for both KD (odds ratio 1.71) and for development of CAAs (odds ratio 1.46), suggesting a potential role in disease susceptibility, but not statistically significant. SNP rs2796817 of the TGFB2 gene correlated with the development of CAAs- the GT/GG genotype showing 8 times higher odds for CAAs, compared to the TT genotype. Conversely, SNP rs6494633 of the SMAD3 gene did not demonstrate a significant association with KD or development of CAAs. However, the odds ratio suggested a lower likelihood of KD in individuals with the A allele, while the same allele showed a higher, though statistically insignificant, odds ratio for the development of CAAs. SNP rs1495592 of TGBR2 gene revealed a notable odds ratio of 0.31, implying a 69% lower chance of developing KD in individuals with the CT/TT genotype. However, this polymorphism did not show a significant association with CAAs. SNP rs795430 of TGFBR2 gene did not emerge as a significant risk factor for KD or development of CAAs. SNP rs12901071 of SMAD3 gene also did not exhibit a significant association with the risk for KD or development of CAAs.

Conclusion:

Our results suggest that SNPs rs1438386 of SMAD3 gene and SNP rs2796817 of TGFB2 gene may have a role in the pathogenesis of KD and development of CAAs. However, this is a single centre study and results need to be replicated from other centres before definitive conclusions can be drawn.