Single nucleotide polymorphisms (rs3736228 and rs4988321) in low-density lipoprotein receptor-related protein-5 gene with predisposition to rheumatoid arthritis.

Background: LRP5 (Lipoprotein Receptor 5) is one of the representatives of the low-density lipoprotein receptors family that play a crucial role in the process of bone homeostasis and bone remodeling. The role of LRP5 single nucleotide polymorphisms (SNPs) rs3736228 and rs4988321 has been associated with the susceptibility to osteoporosis and bone fracture. The frequency of mentioned LRP5 SNPs is unknown among RA (Rheumatoid Arthritis) patients. The case-control study was designed to determine the association of targeted SNPs among RA patients.

Methodology: Patients were selected by ACR/EULAR 2010 criteria. After ethical approval blood samples of patients and healthy individuals were collected. DNA was extracted from the whole blood followed by amplification of the targeted region by T-ARMS PCR (Tetra-primer Amplification Refractory Mutation System) obtained product was observed on agarose gel electrophoresis. The data were analyzed by statistical and bioinformatic tools.

Results: It was observed that the SNPs rs3736228 and rs4988321 showed significant association with the risk of RA [χ = 44, p =< 0.001, O.R 95 % CI = 2.495, (1.865 ∼ 3.337), p =< 0.001] and [χ = 85, p =< 0.001, O.R 95 % CI = 2.05, (1.571 ∼ 2.69), p =< 0.001] respectively. Haplotypes AT, GC, and GT were found to be significantly associated with the risk of RA. Furthermore, both SNPs were in 40 % LD (Linkage Disequilibrium).

Conclusions: The study revealed that SNPs rs3736228 and rs4988321 were significantly associated with the increased susceptibility to RA. The study serves as the baseline data considering targeted SNPs and their association with the progression of the disease. The study might be utilized for the development of potential biomarker for diagnostic purposes and in the precision medicine approach.