Title Page

Contents

ABBREVIATION 10

ABSTRACT 12

1. INTRODUCTION 14

2. BACKGROUND 16

2.1. The fatty acid desaturase (FADS) gene 16

2.2. Polyunsaturated fatty acids 18

2.3. The FADS gene and PUFA 19

2.4. The FADS gene and CAD 21

2.5. Desaturase activity and biological effects 22

3. SUBJECTS AND METHODS 24

3.1. Study subjects 24

3.2. Genotyping of FADS1 rs174547 25

3.3. Blood pressure (BP) and ba-PWV 25

3.4. Anthropometric parameters 26

3.5. Fasting blood collection 26

3.6. Plasma lipid profile and fasting glucose 27

3.7. Serum fating glucose and insulin levels 27

3.8. Fatty acid concentrations based on gas chromatography-mass spectrometry (GC-MS) 28

3.8.1. Chemicals and materials 28

3.8.2. Sample preparation for GC-MS analysis 28

3.8.3. GC-MS analysis 29

3.9. Statistical analysis 30

4. RESULTS 31

4.1. Frequency of the FADS1 rs174547 T〉C polymorphism in normal-weight subjects and overweight subjects 31

4.2. D5D activity, plasma AA levels, the EPA/AA ratio and ba-PWV according to the FADS1 rs174547 T〉C genotype at baseline and at the 3-year follow-up in the normal-weight and overweight groups 32

4.3. Clinical characteristics and biochemical parameters according to the FADS1 rs174547 T〉C genotype at baseline and the 3-year follow-up in the normal-weight and overweight groups 35

4.4. Plasma fatty acid concentrations according to the FADS1 rs174547 T〉C genotype at baseline and at the 3-year follow-up in the normal-weight and overweight groups 39

4.5. Correlation among changes in ba-PWV, clinical characteristics, D5D activity, D6D activity, AA/LA ratio and EPA/AA ratio 43

5. DISCUSSION 47

REFERENCES 51

국문요약 57

Table 1. Association of rs174547 genotypes with clinical and biochemical characteristics at baseline and 3-year follow-up... 36

Table 2. Association of rs174547 genotypes with plasma fatty acids levels at baseline and 3-year follow-up according to BMI. 40

Figure 1. Structure of the FADS1-FADS2 gene cluster 17

Figure 2. The n-3 and n-6 fatty acid metabolism pathway 20

Figure 3. Effect of the rs174547 genotype on changes in delta-5-desaturase activity,... 34

Figure 4. Metabolic pathway analysis of all subjects. Correlation matrix for the changes in clinical parameters,... 45

Figure 5. Correlation between the changes (△) in ba-PWV and the EPA/AA ratio... 46