ABC | Volume 111, Nº1, July 2018

Original Article Pereira et al. Genes and coronary artery disease risk Arq Bras Cardiol. 2018; 111(1):50-61 Figure 2 – Distribution of genetic risk score in deciles by cases and controls.A logistic regression model was used with the 5 th decile of the controls as the reference class. GRS distributions in Deciles 16.0 14.0 12.0 10.0 8.0 6.0 4.0 2.0 0.0 Individuals (%) 3.0 2.5 2.0 1.5 1.0 0.5 0.0 OR Cases Controls OR 1º 2° 3° 4° 5° 6° 7° 8° 9° 10° 6.8 13.7 0.61 8.4 11.9 0.87 9.0 11.3 0.97 9.5 10.5 1.10 9.1 11.1 1 10.7 9.2 1.42 10.7 9.2 1.43 10.9 9.1 1.47 12.1 7.6 1.96 13.0 6.4 2.47 Table 3 – Multivariate analysis performed with the multiplicative genetic risk score (MGRS) (quartiles) and traditional risk factors Variables OR* (95% CI) p value OR + (95% CI) p value MGRS (Quartiles) ------ ------ ------ < 0.0001 2 nd 1.355 (1.082 – 1.698) 0.008 1.406 (1.107 – 1.786) 0.005 3 rd 1.934 (1.539 – 2.429) < 0.0001 2.006 (1.575 – 2.554) < 0.0001 4 th 2.727 (2.162 – 3.439) < 0.0001 2.657 (2.083 – 3.389) < 0.0001 Smoking 3.440 (2.887 – 4.100) < 0.0001 3.651 (3.030 – 4.401) < 0.0001 Diabetes 3.138 (2.559 – 3.847) < 0.0001 3.436 (2.763 – 4.273) < 0.0001 Hypertension 2.067 (1.744 – 2.450) < 0.0001 2.187 (1.816 – 2.633) <0.0001 Dyslipidemia 1.298 (1.023 – 1.646) 0.032 1.344 (1.044 – 1.731) 0.022 Constant 0.186 < 0.0001 Using forward Wald method (SPSS vs. 19.0); Dyslipidemia. Controls: LDL > 140 mg/dL, HDL < 40 mg/dL for men and < 45 mg/dLfor women; triglycerides> 150 mg/dL, APO B > 100 mg/dL. Cases: LDL > 100 mg/dL; triglycerides > 150 mg/dL, HDL < 40 mg/dL for men and < 45 mg/dL for women; APO B > 100 mg/dL, non HDL > 130 mg/dL; OR*: odds ratio adjusted for age and gender; OR + : odds ratio adjusted for gender, age, heart rate, pulse wave velocity, sedentary life style, alcohol, body mass index and family history; CI: confidence interval; Statistically significant for p < 0.05. NRI was also computed using categorical variables and applied to this case-control study and was defined as the percentage of subjects changing categories in each subgroup when adding the new marker (CAD quartile score). Movement towards a better category (higher in patients than in controls) was calculated to address a potential impact for clinical use. NRI showed higher improvement capacity in reclassifying 19.5% of patients from the 50-75% category to the highest risk (75-100%) category. Likewise, 14.1% of healthy controls were moved down into a lower risk category, from 25-50% risk category to < 25% one (Table 5). Furthermore, the inclusion of GRS quartiles to TRF also provided an IDI of 2.5% (95%CI: 1.9-3.1%; p < 0.0001) (data not shown). Discussion Several years ago, polymorphisms involved in specific biological pathways, relevant to coronary atherosclerosis, were genotyped to determine their association with CAD. This candidate gene approach revealed about 30 high-confidence SNPs loci with significant effects on atherosclerosis. 13 However, following traditional candidate gene approach has generated many conflicting results or with weak associations; replication studies are necessary for consistent validation of these results. In 2004, Mendonça et al. first genotyped a ngiotensin - converting enzyme (ACE) I/D polymorphisms in a Portuguese population yielding similar reports as described in literature. 14 55