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

<b>Introduction.</b> Host genetics plays a pivotal role in determining disease susceptibility among individuals infected with <i>Mycobacterium tuberculosis</i>. Scavenger receptors (SRs) such as <i>CD36</i> and <i>SR-B1</i> mediate pathogen recognition and lipid uptake, both of which are central to mycobacterial entry and immune modulation.<b>Gap Statement.</b> Polymorphisms rs1761667 and rs3211938 in <i>CD36</i> and rs4238001 in <i>SR-B1</i> have not been investigated in any population in relation to both latent tuberculosis infection (LTBI) and active tuberculosis (TB).<b>Aim.</b> To genotype <i>CD36</i> and <i>SR-B1</i> 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.<b>Methodology.</b> 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.<b>Results.</b> The homozygous AA genotype of <i>SR-B1</i> rs4238001 was strongly associated with active TB (<i>P</i>=0.00), while the heterozygous GA genotype showed a protective association with LTBI (<i>P</i>=0.00). For <i>CD36</i>, the homozygous GG genotype of rs3211938 was associated with protection against active TB (<i>P</i>=0.02) but exhibited the opposite pattern in LTBI (<i>P</i><0.00). Moreover, the heterozygous GA genotype of rs1761667 was significantly linked to increased risk of LTBI (<i>P</i>=0.00). <i>In silico</i> 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.<b>Conclusion.</b> Polymorphisms in <i>SR-B1</i> and <i>CD36</i> 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.