| Summary: | 博士 === 國立中興大學 === 獸醫學系暨研究所 === 105 === The first topic of this thesis is about the gene polymorphism of rheumatoid arthritis (RA). MUTYH glycosylase directly interacts with various proteins involved in DNA repair pathways and may be associated with the risk of autoimmune diseases such as RA. Therefore, the association between polymorphisms in the MUTYH gene and RA was evaluated. We recruited 192 RA patients and 192 healthy subjects in Taiwan. The 4 MUTYH polymorphisms were detected by a polymerase chain reaction-restriction fragment length polymorphism technique. Haplotype analysis was performed using unphased genotype data using the Bayesian method. The genotype and allelic frequency distributions of the polymorphisms in both RA patients and healthy patients were compared by the chi-square test. Comparison of the genotype/allele frequencies between individuals with RA and the control groups revealed significant differences in 2 MUTYH gene polymorphisms, rs3219463 and rs3219476. The haplotype frequencies were estimated among the 4 identified polymorphisms. After we performed a haplotype-specific analysis, the haplotypes Ht6-GTGC and Ht8-GGCG had lower presenting rates in RA patients than in the control groups. The genotype frequency of rs3219463 G/- was significantly increased among patients with immunoglobulin M rheumatoid factors, whereas that of rs3219476 was not. We demonstrated that the rs3219463 and rs3219476 polymorphisms in RA patients from a Taiwan Chinese population were associated with disease susceptibility. These data indicate that the MUTYH gene may play a role in the progression of RA.
The second topic of this thesis is about the relationship between myopia and inflammation. The prevalence of myopia has rapidly increased in recent decades and has led to a considerable global public health concern. In the Chapter 2 and 3, I elucidate the relationship between Kawasaki disease (KD), allergic conjunctivitis and the incidence of myopia, respectively. I used Taiwan’s National Health Insurance Research Database to conduct a population-based cohort study. I identified patients diagnosed with KD or allergic diseases and individuals without these diseases who were selected by frequency matched based on sex, age, and the index year. The Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence intervals for the comparison of the 2 cohorts. Kaplan-Meier analysis was used to measure the cumulative incidence of myopia in the 2 cohorts. The log-rank test was used to test the incidence of myopia in the 2 cohorts. The risk of myopia (hazard ratio, 1.31; 95% confidence interval, 1.08-1.58; P <0.01) was higher among patients with KD than among those in the non-KD cohort, and a significant higher myopia rate was observed in allergic conjunctivitis group. I had further established allergic conjunctivitis rat model by ovalbumin injection and continuously dropping into eyes. Lower refractive error and longer axial length were observed after induction of allergic conjunctivitis. The decrease in refractive error of allergic conjunctivitis eyes were accompanied by an up-regulation of MMP2 and TGF-β and down-regulation of collagen I, which were the major tissue remodeling proteins related to the myopia formation. The expression levels of inflammatory-related transcription factors and inflammatory cytokines were also up-regulated in allergic conjunctivitis eyes. To sum up, I prove that these two inflammatory ocular diseases are correlated with myopia in nationwide case-control study and in animal model. The prevalence of myopia might be eased if inflammation in eye is controlled effectively.
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