Genetic Polymorphisms Of C-type Lectin Receptors In Behcet's Disease And Vogt-Koyanagi-Harada Syndrome In A Chinese Han Population

PART 1 GENETIC POLYMORPHISMS OF C-TYPE LECTIN RECEPTORS IN BEHCET'S DISEASE IN A CHINESE HAN POPULATIONBackground: Behcet's disease(BD)is a well-known multisystem vasculitis,characterized by recurrent uveitis,oral ulcerations,genital ulcerations and typical skin lesions.It often occurs in young adulthood and causes serious disability and significant visual impairment.C-type lectin receptors(CLRs)are a large group of extracellular Metazoan proteins expressed on immune cells that have been classified as pattern recognition receptors(PRRs)which play an important role in the binding of pathogens via their surface carbohydrate structures.C-type lectin receptors(CLRs)have been reported to be involved in several autoimmune diseases.The role of CLRs in(BD)is not yet known.Purposes: To explore whether SNPs of CLRs were associated with Behcet's disease.Methods: A two-stage association study was carried out and a total of766 BD patients and 1674 healthy controls were recruited.Genotyping of14 SNPs of 13 genes in C-type lectin receptors was performed by iPLEX Gold genotyping or polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay.The expression of mannose binding lectin 2(MBL2)and killer cell lectin like receptor C4(KLRC4)was measured by Real-time PCR.Results: Significantly increased frequencies of A allele as well as AA genotype of rs1800450 in MBL2(Pc = 2.50× 10-6,OR=1.494;Pc = 2.24×10-6,OR=2.899;respectively)and TT genotype of rs2617170 in KLRC4(Pc = 2.53×10-6,OR=1.695)and decreased frequencies of GG genotype of rs1800450(Pc = 1.56×10-3,OR=0.689)and C allele as well as CC genotype of rs2617170(Pc = 2.05×10-9,OR=0.664;Pc=1.20×10-5,OR=0.585;respectively)were observed in BD.Functional studies performed in healthy controls showed that rs1800450/GG genotype carriers had a higher MBL2 gene expression in PBMCs than AG carriers.Rs2617170 CC genotype carriers also had a significantly higher KLRC4 gene expression compared with CT/TT carriers.Conclusions: Our study demonstrates that MBL2/rs1800450 and KLRC4/rs2617170 are susceptibility factors for BD in Chinese Hanpopulation.PART 2 GENETIC POLYMORPHISMS OF C-TYPE LECTIN RECEPTORS IN VOGT-KOYANAGI-HARADA SYNDROME IN ACHINESE HAN POPULATIONBackground: Vogt-Koyanagi-Harada(VKH)syndrome is a bilateral granulomatous panuveitis.The major clinical manifestations of VKH syndrome include meningeal irritation,pleocytosis in the cerebrospinal fluid,dysacusis,alopecia,poliosis,and vitiligo.Although the etiology and pathogenesis of VKH syndrome remain unclear,numerous studies have showed that VKH is a T-cell-mediated autoimmune disorder predominantly against melanocytes.C-type lectin receptors(CLRs)are a large group of extracellular Metazoan proteins expressed on immune cells that have been classified as pattern recognition receptors(PRRs)which play an important role in the binding of pathogens via their surface carbohydrate structures.C-type lectin receptors(CLRs)have been reported to be involved in several autoimmune diseases.The role of CLRs in VKH is not yet known.Purposes: To explore whether SNPs of CLRs were associated with VKH syndrome.Methods: A case-control study was carried out and a total of 380 BD patients and 747 healthy controls were recruited.Genotyping of 14 SNPs of 13 genes in C-type lectin receptors was performed by i PLEX Gold genotyping or polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay.Results: The distribution of genotypic frequency of the 14 SNPs in all subjects did not deviate from Hardy–Weinberg equilibrium(HWE;p>0.05).Allelic and genotypic frequency analysis revealed no significant difference between VKH patients and healthy controls for 14 SNPs of 13 genes in C-type lectin receptors(p>0.05).Conclusions: Our study demonstrates that 14 SNPs of 13 genes in CLRs are not susceptibility factors for VKH in a Chinese Han population.