| Systemic lupus erythematosus (SLE) is a generally accepted prototype autoimmune disease. The importance of genetic influences on SLE has been consistently supported by studies of populations, twin concordance rates, and aggregation of disease in families.Up to now, linkage of 16q12 to Systemic lupus erythematosus (SLE) has been confirmed by 3 independent research groups. Our previous study also established linkage of chromosome 16q12 to SLE and suggested that OLF1/EBF-associated zinc finger protein (OAZ) might be a novel candidate susceptibility gene within the 16q interval.In the first phase, SNPs located around positive microsatellite marker D16S517 within OAZ gene were selected and screened for verification by sequencing. 3 new SNPs were discovered, which are rs2292155 (in intron 3), rs2292156 (in intron 3) and rs3803665 (in exon 4, silent mutation).To observe whether single nucleotide polymorphisms (SNPs) within OAZ gene are associated with SLE in Chinese population, eight SNPs located around D16S517 were genotyped by allelic discrimination-PCR (AD-PCR) with the TaqMan universal PCR master mix and ABI Prism 7900 sequence detector (PE Applied Biosystems). TaqMan MGB probes were used for AD. SNP, haplotype and linkage disequilibrium studies were performed by using the Case-control and Transmission Disquilibrium Test (TDT) approach.Results of Case-control association analysis showed: In Chinese population (1) SNP rs1344531 T allele was significantly associated with SLE susceptibility(T allele: SLE patients(47.0%) versus normal controls(38.1%) ;X2=7.300 ,P=0.008,OR(95%CI)=1.441 (1.105-1.878));Genotypic distribution for SNP rsl 344531(CC/CT/TT) differed significantly between SLE patients (25.5%/54.9%/19.6%) and normal controls (38.1 %/47.6%/14.3%) (x2=8.394, P=0.015 ) , CC genotype frequencies decreased significantly in SLE patients ( 25.5% ) ,as compared with normal controls(3 8.1%) (x2=7.976, P=0.005,OR(95%CI)= 0.557(0.370-0.838)) (2) SNP rs1344531 T allele was significantly associated with LN susceptibility (T allele: SLE patients(53.0%) versus normal controls(38.1%); X2=11.769, P=0.001,OR(95%CI)= 1.832 (1.293-2.596)); Genotypic distribution for SNP rs1344531(CC/CT/TT) differed significantly between LN patients (22.9%/48.2%/28.9%) and normal controls ( 38.1 %/47.6%/14.3%)(x2=12.065, P=0.002) .CC genotype frequencies decreased significantly in LN patients (22.9%) ,as compared with normal controls(38.1%) (x2=6.578, P=0.013, OR(95%C1)= 0.481(0.274-0.848) ), TT genotype frequencies increased significantly in LN patients (28.9%) ,as compared with normal controls(14.3%) (x2=9.423, P=0.003, OR(95%CI)= 2.431(1.363-4.334)). No statistical significance was observed between non-LN patients group and normal controls group.(3)Haplotype analysis produced additional support for association. In LN patients, frequencies for some haplotypes containing rsl344531 (rsl420676-rsl344531(C-T) (x2=11.731,P=0.001, OR(95%CI)=1.867(1.302~2.676)),rs3803665-rsl420676-rsl344531(C-C-T) (X2=8.876,P=0.004,OR(95%CI)=1.772(1.213-2.589)),rs2292155-rs3803665-rsl420676-rsl344531(C-C-C-T) (x2=9.962,P=0.002, OR (95%CI)= 1.915(1.274-2.880)) were detected to increase significantly(41.0% versus 27.1% ; 33.3% versus 21.8% ; 27.0% versus 16.2%);while others (rsl344531-rs2080353(C-A) (x2=8.06,P=0.005, OR (95% CI)=0.603(0.424~0.856)), rsl 34453 l-rs2080353-rs933564(C-A-G) (x2=7.929,P=0.006,OR(95%CI)=0.602(0.422~0.859)) decreased significantly(39.5% versus 52.2%; 36.6% versus 49.2%).Although TDT analysis results didn't show correlation between SNPs and SLE, the trend was observed for the preferential transmission of T polymorphism of rsl344531 from parents to offspring. Our results indicate that SNPs within OAZ gene may either confer susceptibility to Lupus Nephritis or have a linkage disequilibrium with the susceptibility gene in Chinese population.SNPs of disease susceptibility gene may have influence on the expression of gene. In the second phase, we detected the mRNA expression of OAZ gene by fluorescence-based TaqMan real time quantitative PCR with...
|
PDF Full Text Request