Nutritional Genomics 의 적 용 김 혜 진 운동재활학술대회

일반적인 식이 Geographic epidemiology Identify and document 기능성 식품 Nutripharmacoligy Bioanalytical profiling Health claims 개인 영양 집단 영양 Molecular nutrition Biomarkers Home test kit Internet dieticians DNA-nutrient database Molecular epidemiology Biotech foods Food as primary prevention Food-drug complexes Consumer insight surveys forecast that 33% of consumers may be collecting and acting on nutrigenomic information by 2010 Emerging science New channels of information Empowered consumers YesterdayTodayTomorrow Information Knowledge Gillies PJ. J Am Diet Assoc. 2003;102:S50 영양학 분야에서의 trend 와 technology

GenesNutrients Nutrigenetics (Polymorphisms) Retrospective Analysis Applied Science Individual Response to Diet Prospective Analysis Discovery Science Nutritional Systems Biology Nutrigenomics (Gene expression ) Molecular Nutrition “Nutrient-Gene Interaction” Gillies PJ. J Am Diet Assoc. 2003;102:S50

Blueprint DNA=genotype Templates RNA synthesis and degradation Building blocks or tools mRNA translation=proteins Protein actions Posttranslational modifications Phenotype outcome Low essential amino acids Retinoids (n-6)(n-3) Phytosterols selenium iron High saturated fat Oxidizel lipid Excess energy Low folate Low antoxidants Iron leucine Fatty acids Lycopene, B vitamins Trace elements High pathology risk Reduced pathology risk Present knowledge in Nutrition, 8 th edition, 2001 Nutrigenomics 영양소들은 여러 종류의 단백질 함량을 조절하여 신체의 기능에 영향을 미칠 수 있 다.

Low promoter activity High promoter activity High diet need for 20/22 C PUFA Low diet need for 20/22 C PUFA Population distribution varying in cis-acting DNA sequences that govern ∆-6 and ∆-5 desaturase expression ∆-6 and ∆-5 rase Promoter activity Present knowledge in Nutrition, 8 th edition, 2001 Nutrigenetics 유전자 다형성이 개개인의 영양소 요구량의 결정인자가 될 수 있다

Nutrigenomics + Nutrigenetics 식이와 질병 사이의 상호작용에 Genetic variation 의 효과를 연구하는 학문 genome, proteome, metabolome 에서 영양소의 효과 를 탐구하는 분야 Nutritional Genomics 미래의 식이 지침 : 개인 맞춤 영양 Gene 과 nutrient 의 상호작용을 질병 예방과 치료에 초점을 맞추어 연구하는 학문

Multifactorial Disease: 심혈관계 질환 질병과 관련하여 측정이 용이한 항목들 (c.g ch, TG, HDL, LDL) 지질 대사에서의 후보 유전자 발굴 Gene-Diet Interaction 임상에서의 Nutritional Genomics 식이 구성 요소특정한 phynotype genetic polymorphism 에 의하여 Curr Opin Lipidol.2004;15:101-8

개개인의 식사요법에 대한 반응의 다양성 유전적 요인들은 개개인의 특정 식이에 대한 반응이 다르게 나타나는 데에 ( “dietary responsive” or “dietary nonresponsive.” ) 기여할 수 있다.

Apolipoprotein A1 gene Apolipoprotein A1 ( 아포지단백질 A1): -HDL 을 구성하는 주요 지단백질 - 세포로부터 콜레스테롤을 제거하고 간으로 수송하는 역할 ( 콜레스테롤 역수송 ) - LCAT 의 주된 활성인자 -75 (G/A) +83 (MspI±)

Effect of PUFA intake on HDL cholesterol levels GGGA/AA G allele=0.835, A allele=0.165 Harmful effect in PUFA rich diet Benefit in PUFA rich diet Am J Clin Nutr 2002;75:38-46

Genetic Variation 5’ to the LIPC gene Hepatic lipase: 혈장의 지단백질이 세포 내로 이동할 수 있도록 TG 와 phospholipids 로 가수분해시켜주는 효소 -250 (G/A) -514 (C/T) -710 (T/C) -763 (A/G)

CT TT CC Highly significant gene-nutrient interaction Dietary fat intake modifies the effects on – 514(C/T) polymorphism on HDL-C TT subjects: an impaired adaptation to higher fat diet (exclusively in animal fat diet but not so for vegetable fat) These deleterious effects of high-fat diet might be prevented by Mediterranean-style diet (higher vegetable fat & plant foods) Information about one’s genotype [Food choices] The type & amount of dietary fat will Support the health of that person The –514 LIPC genotype, dietary fat and HDL-C levels Circulation 2002;

Recruitment DESIGN: Cross-Sectional study CAD patient Inclusion - Angio ≥ 50% occlusion, (1 or more major coronary arteries) or previous MI Exclusion - diabetes, liver disease, renal disease, thyroid disease, or others 446 CAD patients

1 Triglyceride (mg/dL) A/A (n=121) A/G (n=229) G/G (n=96) b b a HDL-cholesterol (mg/dL) A/A (n=121) A/G (n=229) G/G (n=96) LDL particle size (nm) 1 HOMA-IR a a b b a ab ab a A/A (n=121) A/A (n=121) A/G (n=229) A/G (n=229) G/G (n=96) G/G (n=96) A/AA/GG/G Influence of LTA 252A>G genotypes on features of metabolic syndrome in patients with CAD Mean±S.E. Values significantly different (p<0.05) are indicated by different letters based on one-way analysis of covariance (ANCOVA) with a general linear model followed by Bonferroni method with an adjustment for BMI. 1 Tested after log-transformation 1 Adiponectin (µg/mL) a ab b A/A (n=121) A/G (n=229) G/G (n=96)

Personalize Dietary recommendation

Integration of new genetic information into the development of food- based dietary guidelines RDA=Recommended Dietary Allowance, UL=Upper limits Nutritional genomics 연구를 통한 미래의 식이지침 Gillies PJ. J Am Diet Assoc. 2003;102:S50

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