Abstract:
Background: Sarcoidosis is a rare chronic inflammatory disorder affecting multiple organs,
including the lungs, lymph nodes, and eyes with symptoms including granulomas, dry cough, and
shortness of breath. While several genes have been linked to the disease, environmental and other
conditions trigger its onset.
Objectives: To identify genetic variants associated with Sarcoidosis by analysing Minor allele
frequencies (MAF) of BTNL2 and LTA gene polymorphisms and comparing them with healthy
controls to corelate the symptomatic presentation and mutation zygosity of the selected genes
Methods: A literature review was conducted to identify relevant genetic variants linked to
Sarcoidosis in the Asian population, focusing on the NOD2 gene rs104895462 (C>T), LTA gene
rs1041981 (C>A), ANXA11 gene rs1049550 (G>C), and BTNL2 gene rs2076530 (T>C). Blood
samples from 22 patients were collected nationwide and genotyped using optimized Tetra-primer
Amplification Refractory Mutation System (tetra-primer ARMS) and validated using Sanger
sequencing followed by MAF calculation.
Results: Our research identified BTNL2 and LTA, with a high disease prevalence in individuals
aged 40-50 years, of whom 81.81% had lung granulomas. Among (n=13) individuals carrying the
LTA variant, 30.76% were homozygous, while 69.23% were heterozygous with the mutant allele
(MAF 0.4091). In contrast, all 9 individuals carrying BTNL2 variants were heterozygous for the
mutant allele (MAF 0.2045). The previously reported MAF of BTNL2 is 0.3989 and LTA is 0.36.
Our findings strongly associate these genes and sarcoidosis in patients with Sarcoidosis in Sri
Lanka, consistent with other Asian studies. Further, BTNL2 modulate T-cell proliferation, while
LTA regulates tumor necrosis factor collectively promoting granuloma formation via single
nucleotide polymorphisms.
Conclusions: This study successfully optimized tetra-primer ARMS PCR for the selected genes
and reinforced the genetic basis of Sarcoidosis by analyzing MAF, followed by supporting the
involvement of the BTNL2 and LTA genes in observed clinical features.
