Mannan-binding lectin (MBL) is an innate pattern recognition molecule known to play a key role in pathogen clearance. As MBL2 gene polymorphism is associated to an increased susceptibility to infection, we aimed to determine genetic variations in the MBL2 gene in rheumatic heart disease (RHD). Genetic variations in the promoter and exon 1 region of the MBL2 gene were analyzed in 107 patients with RHD and 105 controls by real-time polymerase chain reaction. The frequency of MBL2* A/A genotype was significantly higher in RHD patients (71/107, 66.36% vs 52/105, 49.52%, p<or=0.02, OR=1.99, 95% CI, 1.15-3.50). A/A genotypes were associated with higher levels of MBL in RHD compared with controls with the same genotype (p<or=0.004). The frequency of HYPA/HYPA, HYPA/LYQA, and LYQA/LYQA haplotypes was also increased in RHD (p<or=0.03, OR=1.98, 95% CI, 1.05-3.73). However, the frequency of MBL2 variant alleles (termed "O") was lower among patients (39/214, 18.2% vs 63/210, 30.0%, p<or=0.006, OR=0.52, 95% CI, 0.33-0.82), which was also seen for O/O genotypes (3/107, 2.8% vs 10/105, 9.5%, p<or=0.05, OR=0.27, 95% CI, 0.07-1.03). This data suggests a role for MBL genotypes in the susceptibility to RHD. However, it still remains unclear whether A/A homozygosity is a risk factor for RHD or rheumatic fever itself.