CD36 and SR-B1 polymorphisms exhibit distinct association patterns in active and latent tuberculosis

Introduction. Host genetics plays a pivotal role in determining disease susceptibility among individuals infected with Mycobacterium tuberculosis . Scavenger receptors (SRs) such as CD36 and SR-B1 mediate pathogen recognition and lipid uptake, both of which are central to mycobacterial entry and immune modulation. Gap Statement. Polymorphisms rs1761667 and rs3211938 in CD36 and rs4238001 in SR-B1 have not been investigated in any population in relation to both latent tuberculosis infection (LTBI) and active tuberculosis (TB). Aim. To genotype CD36 and SR-B1 polymorphisms and evaluate their association with TB and LTBI. To predict the functional/regulatory impact of these SNPs and compare their allele frequencies with global datasets. Methodology. Polymorphisms were genotyped using amplification refractory mutation system PCR within a case-control design. Genotype frequencies were compared using Fisher’s exact chi-square test. Functional and regulatory effects were predicted using PolyPhen-2 and RegulomeDB, while the 1000 Genomes database was used for population comparison. Results. The homozygous AA genotype of SR-B1 rs4238001 was strongly associated with active TB ( P =0.00), while the heterozygous GA genotype showed a protective association with LTBI ( P =0.00). For CD36 , the homozygous GG genotype of rs3211938 was associated with protection against active TB ( P =0.02) but exhibited the opposite pattern in LTBI ( P <0.00). Moreover, the heterozygous GA genotype of rs1761667 was significantly linked to increased risk of LTBI ( P =0.00). In silico functional prediction classified rs4238001 as missense and rs3211938 as nonsense variant. Regulatory analysis indicated that rs4238001 and rs1761667 affect transcription in TB-relevant tissues. Population analysis highlighted variation in allele frequencies across groups. Conclusion. Polymorphisms in SR-B1 and CD36 show distinct associations with LTBI and TB, suggesting contrasting genetic influences on infection establishment and disease onset. These findings reveal a novel host genetic component of TB pathogenesis and warrant validation in larger, multiethnic cohorts.