Sex susceptibility of
CFH (I62V) in AU was found in our previous study.
10 In this study, logistic regression analysis showed none of the 5 SNPs had significant interaction with sex, indicating that sex factor in C2 and CFB may not confer analogous effect as CFH. In addition, for HLA-B27-positive patients, significant association was identified with
CFB-rs1048709, where there were significant increased frequencies of A allele and AA homozygosity in HLA-B27-positive patients compared with controls (
Table 2), while for HLA-B27-negative patients, such association could not be detected after correction for multiple testing. Our findings suggested that the influence of
C2 and
CFB polymorphisms on AU differed depending on HLA-B27 status, inconsistent with results of our previous study of
CFH.
10 The exact reason for this discrepancy is unclear, further indicating the complexity of immune regulation in uveitis.
6,10 Moreover, based on our previous study,
6 only 6% of control subjects are HLA-B27 positive, therefore we did not perform stratified analysis of the controls based on HLA-B27 positivity due to the small sample size. To further clarify the association between
CFB-rs1048709 and AU under the condition of HLA-B27, formal hypothesis testing was also performed by comparing the allele and genotype frequency of rs1048709 in AU patients with or without HLA-B27. Our results showed that no significant difference was found between allele frequency and HLA-B27 positivity (
P = 0.06). Also, no significant different was found between genotypic frequency and HLA-B27 positivity (
P = 0.117). The nonsignificant results suggested no association between HLA-B27 and rs1048709 in our study cohort. While the
P value was marginal, the results should be interpreted cautiously, and further investigations are still needed. Meanwhile, stratified analyses according to recurrence and laterality status of AU patients showed that clinical severity did not affect the association of these SNPs on AU.