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Title: A composite scoring of genotypes discriminates coronary heart disesase risk beyond conventional risk factors in the Boston Puerto Rican Health Study

Author
item JUNYENT, MIREIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TUCKER, KATHERINE L. - Northeastern University
item SHEN, JIAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LEE, YU-CHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SMITH, CAREN E. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MATTEI, JOSIEMER - Harvard University
item Lai, Chao Qiang
item Parnell, Laurence
item ORDOVAS, JOSE M. - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Nutrition Metabolism and Cardiovascular Disease
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/13/2009
Publication Date: 1/20/2010
Citation: Junyent, M., Tucker, K., Shen, J., Lee, Y., Smith, C., Mattei, J., Lai, C., Parnell, L.D., Ordovas, J. 2010. A composite scoring of genotypes discriminates coronary heart disesase risk beyond conventional risk factors in the Boston Puerto Rican Health Study. Nutrition Metabolism and Cardiovascular Disease. 20(3):157-164.

Interpretive Summary: Cardiovascular disease risk is defined by a complex combination of genetic and environmental factors. A better knowledge of the genetic component will afford earlier risk prediction and effective prevention using nutritional approaches and other behavioral modification. For this purpose, we have created a genetic predisposition score (GPS), integrating the additive associations of a set of genes involved with Coronary Heart Disease (CHD). We studied 11 genetic polymorphisms at eight genes in 197 subjects with prior CHD and 524 CHD-free subjects from the Boston Puerto Rican Health Study. Our results show that the mean score was higher in participants with prior CHD than those CHD-free. Moreover, the joint presence of a high GPS with more traditional biochemical and clinical risk factors increased CHD risk even further. In conclusion, a genetic score of 11 polymorphisms may identify those subjects at increased risk of CHD beyond conventional risk factors and provide them with early nutritional advice to prevent the expression of the disease.

Technical Abstract: Background and aims: Using a genetic predisposition score (GPS), integrating the additive associations of a set of single nucleotide polymorphisms (SNPs) with CHD, we examined the consequences of the joint presence of a high GPS and conventional risk factors (CRFs). Methods and results: We studied 11 SNPs at eight loci in 197 participants with prior CHD and 524 CHD-free subjects from the Boston Puerto Rican Health Study. Each polymorphism contributed 1 unit (high-risk allele homozygous), 0.5 units (heterozygous) and 0 units (low-risk allele homozygous) to the GPS. Odds ratio (OR) of CHD for those at high risk because of GPS (>5) and simultaneous presence of CRFs were estimated, compared with subjects at low risk, for both measurements. The mean score was higher in participants with prior CHD than those CHD-free (PZ 0.015), and the OR for CHD with a GPS > 5 was 2.90 (P < 0.001).The joint presence of a high GPS and each CRF was associated with higher risk of CHD. Compared to participants with high GPS, those with low GPS (_5) were protected against CHD even if they were smokers (OR Z 0.44), heavy drinkers (OR Z 0.43), displayed low physical activity (OR Z 0.35), had hypertension (OR Z 0.52) or hyperlipidemia (OR Z 0.34) (P values ranging from 0.004 to 0.023). Conclusion: A simple genetic score of 11 polymorphisms may identify those subjects at increased risk of CHD beyond conventional risk factors