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- 1. Prediction of Adult Dyslipidemia Using Genetic and Childhood Clinical Risk Factors The Cardiovascular Risk in Young Finns Study Presented by: Neha Masarkar PhD scholar Department of Biochemistry AIIMS Bhopal. Joel Nuotio, MD*; Niina Pitkänen, PhD*; Costan G. Magnussen, PhD; Marie-Jeanne Buscot, MSc; Mikko S. Venäläinen, MSc; Laura L. Elo, PhD; Eero Jokinen, MD, PhD; Tomi Laitinen, MD, PhD; Leena Taittonen, MD, PhD; Nina Hutri-Kähönen, MD, PhD; Leo-Pekka Lyytikäinen, MD; Terho Lehtimäki, MD, PhD; Jorma S. Viikari, MD, PhD; Markus Juonala, MD, PhD; Olli T. Raitakari, MD, PhD Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland. Circ Cardiovasc Genet, April 25, 2017
- 2. INDEX Introduction Objective Material and Method Results Discussion Conclusion Pilot Study References
- 3. INTRODUCTION: DEFECTS IN LIPID METABOLISM Lipid abnormalities play a vital role in the patho-physiological mechanisms of atherosclerosis and, hence, cardiovascular diseases. Being a modifiable risk factor Lipid levels have the tendency to track from childhood to adulthood. According to various studies, strongest predictors of Dyslipidemia in adulthood are: lipid concentration and BMI (Body mass index) in childhood. Dyslipidemia is a multifactorial disorders of lipids and lipoproteins, characterized by abnormal levels such as elevated Low density lipoprotein (LDL-C), triglycerides, total cholesterol or decreased high density lipoprotein (HDL-C). (Nuotio et. al, 2017)
- 4. Causes: (Liu et al., 2011)
- 5. SINGLE NUCLEOTIDE POLYMORPHISM Single nucleotide polymorphisms: most common type of genetic variation. Represents a difference in a single nucleotide, for example, nucleotide adenine (A) with the nucleotide guanine (G) in a certain stretch of DNA. Although plasma lipid concentrations are strongly influenced by smoking, diet, level of physical activity, and other lifestyles choices, twin and family studies suggest that about 50-80% of the variation is influenced genetically. (Hegele, 2001).
- 6. CLINICAL IMPLICATIONS If preventive measures are not taken, excessive intake of cholesterol is continued, defects in lipid metabolism may lead to Dyslipidemia, which further contributes to Atherosclerosis and other cardiovascular diseases. Thus, early identification of children and adolescents at increased risk could allow targeted prevention strategies earlier in the disease process with the potential to prevent or delay dyslipidemia related complications. (Nuotio et. al, 2017)
- 7. This is a multicentre study, at first called 'Atherosclerosis Precursors in Children' later on renamed to 'Cardiovascular Risk in Young Finns', was designed as a collaborative effort of various university departments. The study is done over a period of >31 years. The first study was done in 1980 when the age of study population was 3-18 years. The cohorts were followed up every three years since 1980.
- 8. OBJECTIVE The main objectives of the base-line study have been to: 1) Study risk factors. 2) Study the determinants of CVD risk factors and the mechanisms by which risk factor levels change into adult levels. 3) Study the effect of the time of the study and age of subjects on the results. 4) Collect background information for future intervention, primary prevention of CVD in Finnish children and adolescents. Objective of this study was to examine whether information on lipid- associated SNPs improves early identification of children and adolescents at increased risk for dyslipidemia in adulthood using data from the prospective follow-up of participants since childhood in the Cardiovascular Risk in Young Finns Study.
- 9. MATERIAL AND METHODS Study Population:- The baseline study included 3596 children and adolescents aged 3-18 years (from Helsinki, Kuopio and Turku ), who were followed up every 3 year. Written informed consent was obtained from all participants or their parents. The study was approved by local ethics committees in agreement with the Declaration of Helsinki. YEAR Participants 1980 3596 1992 2370 2001 2283 2011 2443 2017 2422
- 10. SUMMARY OF DATA ITEMS IN THE CARDIOVASCULAR RISK IN YOUNG FINNS STUDY Cardiovascular risk factors Anthropometry: Weight, Height, BMI, Skinfold thickness (sub-scapular, biceps and triceps), Waist and hip circumference. Smoking Blood pressure Biochemistry: Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglyceride Nutrition: Frequencies of consumption of selected foods Nutrient intake and food consumption Food behavior Socioeconomy Parental occupational status, Study subject’s education and occupational status.
- 11. Cardiovascular risk factors Physical activity Psychology: Parental job stress, life satisfaction, parent-child attachment and child rearing practices Subject’s innate temperament, self esteem and social adjustment Temperament, depression, hostility and social support since Job stress and social attachment. Autonomic nervous function: Heart rate variability. Bone density measurements DXA-measurements. DNA Over 300 genes studied. Measures of sub-clinical atherosclerosis Carotid artery IMT.
- 12. Cardiovascular risk factors Genotyping 156 genetic polymorphisms Statistical analysis wGRS.
- 13. SNP’s included in the study RESULTS
- 17. WEIGHTED GENETIC RISK SCORE For many diseases, genetic influences cannot be explained by simple Mendelian modes of inheritance only. Moreover, genetic and environmental factors may jointly contribute to susceptibility (gene-environment GxE interaction). Since most complex diseases are influenced by hundreds of genetic variants each having a small effect on its own, its feasible to combine the variations. The most common approach is the weighted genetic risk score (GRS) approach in which a weighted GRS is calculated from a pre-selected number of genetic variants to define a person’s individual genetic risk for disease development. More the risk score more is the susceptibility.
- 18. WEIGHTED GENETIC RISK SCORE The wGRS for HDL-C ranged from −3.42 to 3.13 in individuals with low HDL-C and −3.01 to 3.10 in individuals with high HDL-C. The wGRS for LDL-C ranged from −3.02 to 3.50 in individuals with high LDL-C and −3.17 to 4.20 in individuals with low LDL- C. The wGRS for triglycerides ranged from −2.34 to 3.86 in individuals with high triglycerides and −3.13 to 3.34 in individuals with low triglycerides.
- 19. Prevalence of elevated Cholesterol levels in adulthood according to childhood cholesterol levels and weighted genetic risk scores 1 2 3 4 1: Normal cholesterol, Low wGRS 2: Normal cholesterol, High wGRS 3: High cholesterol, Low wGRS 4: High cholesterol, High wGRS
- 20. In the baseline studies results suggested that exposure to cardiovascular risk factors in early in life may induce changes in arteries. For example, exposure to high LDL cholesterol, elevated blood pressure, obesity and cigarette smoking in adolescence predict increased carotid IMT and decreased elasticity in later adulthood. 45% of individuals with low genetic risk and cholesterol levels in childhood had elevated cholesterol in adulthood. Participants with both elevated cholesterol levels in childhood and high genetic risk had clearly highest risk for adult dyslipidemia, as 92% of these individuals had elevated choleserol levels in adulthood.
- 21. DISCUSSION In this study, it observed that the prediction of adult dyslipidemia can be improved significantly by incorporating lipid-specific genetic risk scores. In the present study, using genetic risk scores based on 157 SNPs, it was observed that the lipid-specific genetic risk scores improve significantly the risk discrimination of adult dyslipidemia compared with clinical childhood lipid measures. The results were found that genetic information provides incremental information compared with clinical risk factors in identifying children and adolescents who are at risk of developing dyslipidemia in adulthood. As atherosclerosis has its roots in childhood, early identification and control of dyslipidemia throughout the life span would reduce the risk for later clinical CVD.
- 22. CONCLUSIONS Childhood lipid levels and lipid-specific genetic risk scores were independently related to dyslipidemia in adulthood 31 years later. The inclusion of wGRS to lipid-screening programs in childhood could modestly improve the identification of those at highest risk of dyslipidemia in adulthood.
- 23. A STUDY OF POLYMORPHISM OF GENES ASSOCIATED IN LIPID METABOLISM BASIS FOR DYSLIPIDEMIA IN UNSELECTED POPULATION OF MADHYA PRADESH Neha Masarkar, Rashmi Chowdhary, Sagar Khadanga, S.K. Goel Department of Biochemistry, All India Institute of Medical Sciences, Bhopal. INTRODUCTION: Dyslipidemia is a multifactorial disease in which lipoproteins plays an important role. The plasma concentrations of lipoproteins and their metabolic fates are modulated by apolipoproteins. Studies identify that SNP in APOC3 and FABP2 genes predispose individuals to Dyslipidemia. Fatty acid-binding protein 2 (FABP 2) is responsible for transport of free fatty acids in the intestinal endothelium cells. Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase. OBJECTIVE: The aim of this study was to investigate the association between FABP2 Ala54Thr and APOC3 rs5128 genetic polymorphism and Dyslipidemia in population of Madhya Pradesh, and its association with occurrence of cardio vascular diseases (CVD).
- 24. METHODOLOGY: Total 90 subjects (30 Diabetic Dyslipidemics, 30 Non-Diabetic Dyslipidemics and 30 controls) were included. Biochemical analysis, genomic DNA isolation was done. Genotyping was done by PCR-RFLP. Statistical analysis using Graph-Pad and SPSS was done. RESULTS: Our data indicated that APOC3 and FABP2 polymorphisms are associated with Dyslipidemia, and disease associated (CVD) prominently in Non-Diabetic Patients. Further studies are required for more accurate results.
- 25. REFERENCES Hegele R.E., 2001, Monogenic Dyslipidemias: Window on Determinants of Plasma Lipoprotein Metabolism, Am. J. Hum. Genet., 69:1161–1177. Juonala M, Viikari JS, Hutri-Kähönen N, Pietikäinen M, Jokinen E, Taittonen L, Marniemi J, Rönnemaa T, Raitakari OT., 2004, The 21- year follow-up of the Cardiovascular Risk in Young Finns Study: risk factor levels, secular trends and east-west difference. J Intern Med., 255(4):457-68. LiuY, Zhou D, Zhang Z, Song Y, Zhang D, Zhao T, Chen Z, Sun Y, Zhang D, Yang Y, Xing Q, Zhao X, Xu H, and He L, 2011, Effects of genetic variants on lipid parameters and dyslipidemia in a Chinese population, J Lipid Res., 52(2): 354–360.