Novel Variants and Haplotypes are Associated with Rheumatic Heart Disease.

Ficolins are pattern recognition molecules that are involved in innate immune defense. Ficonin-2 (FCN2) has a specific affinity for lipoteichoic acid present in the cell wall of , an etiological agent for rheumatic heart disease (RHD). We have estimated FCN2 serum levels and analyzed the functional variants of in 400 RHD patients, 617 healthy controls, and 581 individuals belonged to various ethnic populations, who are inhabited in various geographical regions of India. Our study revealed that the -986A and +6359T alleles were the risk factors for RHD susceptibility ( = 0.0007 for -986G>A;  = 0.0004 for +6359C>T). The haplotype AGGT ( = 0.0024) was observed to be a risk factor for RHD susceptibility, and the haplotype GGAC ( = 0.002) was found to confer protection against RHD. The level of serum FCN2 was significantly higher in controls ( < 0.0001) and in controls with GGAC haplotypes ( < 0.0001). The frequency of the risk alleles -986A and +6359T was found to be more prevalent in Northern and North-Western (Indo-European) India. The protective GGAC haplotype was found more prevalent in Eastern (Tibeto-Burman) and South-Western (Dravidian) India. Alleles -986A and +6359T were in positive correlation with the prevalence of RHD (regression coefficient = 1.84 and 1.94, respectively), whereas GGAC haplotype was in negative correlation with prevalence of RHD (regression coefficient = -1.71). In conclusion, we found that low level of serum ficolin-2 is significantly associated with RHD. Further, -986A and +6359T alleles and AGGT haplotype are associated with increased susceptibility to RHD, while GGAC haplotype is associated with moderate protection against RHD.