Association and Polymorphism of Human Leukocyte Antigen HLA Class II Alleles and Lectin Complement Pathway Components in Rheumatic Heart Disease Patients of North East India

Abstract

The various reports have documented the role of HLA in RHD but still there is a dearth of information in Indian population and no investigation has been done in North-East Indian population. Beside HLA, lectin complement system components (MBL2, FCN2 and MASP2) have been associated with increased risk towards RHD but no information is available from North-East India. So, our attempt is to find out the nexus between HLA class II alleles and lectin complement pathway components in RHD cases of North-East Indian population to elucidate the influence of these molecules in susceptibility and progression of RHD. newlineIn the present study, socio-economic profile of the RHD patients was analyzed. Also, we performed HLA typing to find out the predominant HLA alleles in RHD patients enrolled in Assam Medical College and Hospital (AMCH), Assam and equal number of healthy controls were also analyzed. Further, the predominant HLA allele (HLADRB1*15:01:03) was amplified and sequenced to find out single nucleotide polymorphism (SNP) associated with RHD. Lectin complement proteins (MBL2,FCN2 and MASP2) were also amplified and sequenced for the analysis of SNPs. newlineAdditionally, we investigated the effect of SNPs on the structural and functional newlinepotential of HLA using bioinformatics tools. Collectively, we observed that socio-economic factors are significantly associated with enhanced risk of RHD in Assam. HLA-DRB1*15:01:03 allele was found to be predominant in this population and three SNPs were observed in this allele. In silico analysis confirmed the deleterious impact of amino acid substitutions in binding and non-binding region of HLA-DRB1*15:01:03. Also, MBL2, FCN2 and MASP2 newlinepolymorphisms were found to be associated with decreased serum level of these newlineproteins. Overall, our results exemplify that socio-economic status is a compelling feature in increased risk of RHD while HLA and lectin complement system proteins participate in pathogenesis and progression of RHD. newline