Title Page

Contents

ABBREVIATIONS 10

ABSTRACT 12

1. INTRODUCTION 15

2. BACKGROUND 17

2.1. Korean Chip 17

2.2. MACROD2 gene 18

2.2.1. Previous researches on the MACROD2 gene 18

2.2.2. MACORD2 rs6110695 A＞G polymorphism 19

2.3. Total blood cell count 20

2.3.1. Previous researches on associations between WBC count and chronic diseases 20

2.3.2. Subtype of total blood cell count as a potential biomarker for chronic diseases 20

2.4. WBC to apolipoprotein A-I ratio 22

2.5. Interferon (IFN)-γ 22

3. METHODS 24

3.1. Study population 24

3.2. Blood sample collection 25

3.3. Anthropometric measurement 25

3.4. Biochemical characteristic assessment 26

3.5. Total blood cell count and cytokine levels assessment 27

3.6. SNP genotyping array 28

3.7. Statistical analysis 29

4. RESULTS 31

4.1. Analyses of clinical/biochemical characteristics and total blood cell count/cytokine levels according to the rs6110695 genotypes 33

4.2. An optimal cut-off value of WBC count 36

4.3. Distribution of the rs6110695 genotypes 38

4.4. Analyses clinical/biochemical characteristics and total blood cell count/cytokine levels according to the WBC cut-off value 40

4.5. Subanlayses of clinical/biochemical characteristics and total blood cell count/cytokine levels in rs6110695 AA and AG genotype groups stratified from the WBC ≥5.450 group 42

5. DISCUSSION 45

6. CONCLUSION 51

REFERENCES 52

APPENDIX 61

Table S1. Clinical and biochemical characteristics in the study participants according to the WBC cut-off value. 61

Table S2. Total blood cell count and cytokine levels in the study participants according to the WBC cut-off value. 62

국문요약 63

Table 1. Clinical and biochemical characteristics in the study participants according to the rs6110695 genotypes. 34

Table 2. Total blood cell count and cytokine levels in the study participants according to the rs6110695 genotypes. 35

Table 3. Frequencies of the rs6110695 genotypes according to the WBC cut-off value. 39

Table 4. Clinical and biochemical characteristics in the study participants according to the rs6110695 genotypes in the WBC ≥5.450 group. 43

Table 5. Total blood cell count and cytokine levels in the study participants according to the rs6110695 genotypes in the WBC ≥5.450 group. 44

Figure 1. Manhattan plot and top 5 SNPs associated with WBC. 32

Figure 2. Optimal cut-off value of WBC count to estimate rs6110695 genotypes. 37