Association between Genetic Variations of MERTK and Chronic Obstructive Pulmonary Disease in Koreans

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regarding the genetic susceptibility of Koreans to this disease. MER receptor tyrosine kinase (MERTK) plays important roles in the inhibition of inflammation and in the clearance of apoptotic cells. Here, we investigated the association between genetic variations in MERTK and the development of COPD in Koreans. METHODS: We conducted genetic analysis of MERTK using genomic DNA samples from 87 patients with COPD and 88 healthy controls and compared the frequency of each variation or haplotype between the patient and control groups. Subsequently, the effect of each variation was evaluated using in vitro assays. RESULTS: Ten variations were identified in this study, four of them for the first time. In addition, we found that the frequency of each variation or haplotype was comparable between the patient and control groups. However, we observed that the frequency for the wild-type haplotype was higher in the control group, compared to that in the group of patients with COPD, in the subgroup analysis of current smokers, although the difference was not statistically significant (P = 0.080). In in vitro assays, we observed that none of the variations affected the activity of the promoter or the expression of MERTK. CONCLUSION: Our findings indicate that the susceptibility to COPD is not related to the genetic variations or haplotypes of MERTK in Koreans.

Identification and Functional Characterization of ST3GAL5 and ST8SIA1 Variants in Patients with Thyroid-Associated Ophthalmopathy

PURPOSE: This study was conducted to identify and to functionally characterize genetic variants in ST3GAL5 and ST8SIA1 in Korean patients with thyroid-associated ophthalmopathy (TAO). MATERIALS AND METHODS: Genetic analyses were conducted using DNA samples from TAO patients (n=50) and healthy subjects (n=48) to identify TAO-specific genetic variants of ST3GAL5 or ST8SIA1. The effect of each genetic variant on the transcription or expression of these genes was examined. Additionally, correlations between functional haplotypes of ST3GAL5 or ST8SIA1 and clinical characteristics of the patients were investigated. RESULTS: Six promoter variants and one nonsynonymous variant of ST3GAL5 were identified, and four major promoter haplotypes were assembled. Additionally, three promoter variants and two major haplotypes of ST8SIA1 were identified. All ST3GAL5 and ST8SIA1 variants identified in TAO patients were also found in healthy controls. Promoter activity was significantly decreased in three promoter haplotypes of ST3GAL5 and increased in one promoter haplotype of ST8SIA1. Transcription factors activating protein-1, NKX3.1, and specificity protein 1 were revealed as having roles in transcriptional regulation of these haplotypes. The nonsynonymous variant of ST3GAL5, H104R, did not alter the expression of ST3GAL5. While no differences in clinical characteristics were detected in patients possessing the functional promoter haplotypes of ST3GAL5, exophthalmic values were significantly lower in patients with the ST8SIA1 haplotype, which showed a significant increase in promoter activity. CONCLUSION: These results from genotype-phenotype analysis might suggest a possible link between the ST8SIA1 functional promoter haplotype and the clinical severity of TAO. However, further studies with larger sample sizes are warranted.