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Atherogenesis and dyslipidemia increase the risk of cardiovascular disease, which is the leading cause of death in developed countries. While blood lipid levels have been studied as disease predictors, their accuracy in predicting cardiovascular risk is limited due to their high interindividual and interpopulation variability. The lipid ratios, atherogenic index of plasma (AIP = log TG/HDL-C) and the Castelli risk index 2 (CI2 = LDL-C/HDL-C), have been proposed as better predictors of cardiovascular risk, but the genetic variability associated with these ratios has not been investigated. This study aimed to identify genetic associations with these indexes. The study population (n = 426) included males (40%) and females (60%) aged 18–52 years (mean 39 years); the Infinium GSA array was used for genotyping. Regression models were developed using R and PLINK. AIP was associated with variation on APOC3, KCND3, CYBA, CCDC141/TTN, and ARRB1 (p-value < 2.1 × 10−6). The three former were previously associated with blood lipids, while CI2 was associated with variants on DIPK2B, LIPC, and 10q21.3 rs11251177 (p-value 1.1 × 10−7). The latter was previously linked to coronary atherosclerosis and hypertension. KCND3 rs6703437 was associated with both indexes. This study is the first to characterize the potential link between genetic variation and atherogenic indexes, AIP, and CI2, highlighting the relationship between genetic variation and dyslipidemia predictors. These results also contribute to consolidating the genetics of blood lipid and lipid indexes.

Introduction: Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin. Methods: HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach. Results: We identified genetic variants on SLC47A1, SLC28A1, ABCG2, TBC1D4, and ARID5B that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis. Conclusions: Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.

Angiotensin-converting enzyme 2 (ACE2) is known as the counter-regulator of the renin-angiotensin system, it cleaves angiotensin II to render Ag 1-7, a potent vasodilator with multiple roles in cardiovascular protection. A few studies have pinpointed ACE2 polymorphisms and their relationship with heart function and hypertension in a sex-dependent manner. These observations still lack replication mostly for admixed populations. This study aimed to report minor allele frequencies of four ACE2 intron variants, rs2285666, rs2048683, rs2106809, and rs4240157, derived from previous research using the GSA, v1.0, microarray in 1231 hypertensive and nonhypertensive patients. Logistic and multiple linear regression models were developed to identify potential associations with hypertension status and systolic and diastolic blood pressure (SBP and DBP). Allele frequency differences were identified for ACE2 rs2048683 and rs4240157 in populations with European ancestry and people of the Americas. Regression analyses identified a significant association of ACE2 rs2048683 and rs4240157 with SBP/DBP in males or females. Our observations confirm sex differences in ACE2 genetic associations with SBP and DBP and contribute to the collection of genetic variation in ACE2 for admixed populations.

Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin.HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach.We identified genetic variants on SLC47A1, SLC28A1, ABCG2, TBC1D4, and ARID5B that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis.Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.