Search Results (67)

Background: Coarctation of the aorta (CoA) is a congenital narrowing of the aortic isthmus near the ductus arteriosus or ligamentum arteriosum. Despite successful anatomical repair, patients remain at risk of recoarctation, arterial hypertension, and diffuse aortopathy, suggesting intrinsic vessel-wall abnormalities beyond localized obstruction. The developmental and molecular basis of these persistent vascular features remains incompletely understood. Methods: Human aortic tissue samples were obtained from 8 male infants with CoA and 6 age- and sex-matched controls aged <1 year. Total RNA was isolated, and gene expression profiling was performed using whole human genome oligo microarrays (Agilent). Differentially expressed transcripts were subjected to pathway, network, and upstream regulator analyses using Ingenuity Pathway Analysis (IPA, Qiagen). Selected candidate genes were evaluated by RT-qPCR in independent verification sets. Results: Transcriptomic profiling identified 402 analysis-ready transcripts distinguishing CoA from control tissue. Exploratory pathway analyses suggested extracellular matrix remodeling characterized by collagen turnover, integrin-mediated cell–matrix interactions, wound-healing signaling, and fibrosis-associated programs. In addition, enrichment analyses identified developmental annotations involving retinoic acid (RA)/RAR/RXR signaling, HOX-associated developmental programs, and a shared HOX/MEIS-associated signature. Network and upstream regulator analyses further suggested associations with cytoskeletal, muscle-associated, and epigenetic regulatory pathways, including KAT6A, KAT6B, retinoic acid/RAR/RXR signaling, DNMT3B, KMT2A, and ARID1A. RT-qPCR independently confirmed increased expression of EDN1, AGTR2, IRS4, and TFAP2B.Conclusions: Infantile CoA tissue exhibited molecular signatures consistent with vessel-wall remodeling accompanied by developmental, vascular signaling, and smooth muscle/cytoskeletal regulatory programs. These findings support the hypothesis that developmental patterning signals and postnatal extracellular matrix remodeling coexist within CoA tissue and may contribute to persistent vascular abnormalities beyond anatomical repair. Given the exploratory nature of the study, these observations should be considered hypothesis-generating and require validation in independent cohorts. Full article

Differential fecundity in goats is a complex trait governed by coordinated molecular regulation across reproductive and endocrine tissues. In this study, we performed integrated metabolomic profiling of follicular fluid, serum, thyroid tissue, and uterine luminal fluid together with transcriptomic sequencing of follicular, thyroid, and uterine horn tissues from high-fecundity (HF) and low-fecundity (LF) Yangtze River Delta White goats. In addition, weighted gene co-expression network analysis (WGCNA) was conducted to elucidate the molecular mechanisms underlying differential litter size. High-fecundity goats exhibited enhanced follicular steroidogenesis, superior corpus luteum function, and more stable hypothalamic–pituitary–thyroid (HPT) axis activity, accompanied by increased uterine gland density and greater myometrial thickness. Metabolomic profiling identified 6640 metabolites displaying tissue-specific differential abundance patterns. Pathway enrichment analysis highlighted steroid hormone biosynthesis and energy metabolism in follicular fluid, PPAR signaling and tyrosine metabolism in thyroid tissue, and glycerophospholipid and one-carbon metabolism in uterine luminal fluid as major pathways associated with fecundity. Transcriptomic analysis identified 1596 differentially expressed genes (DEGs), including 20 genes shared across all examined tissues, constituting a systemic molecular signature associated with fecundity. WGCNA further revealed three functional tissue axes associated with follicular development (ELOVL4, INHA, NR5A2), thyroid endocrine regulation (GRHL2, NAPRT), and uterine receptivity (RSPO1, AGTR2, PTGER3). Low-fecundity-associated modules were predominantly concentrated in follicular and thyroid tissues, whereas the high-fecundity-specific module was mainly enriched in uterine horn. These findings provide a multi-tissue molecular framework underlying differential fecundity in goats and identify candidate hub genes and metabolites that may serve as candidate biomarkers for fecundity assessment and selective breeding programs. Full article

Background/Objectives: Glucocorticoids, including dexamethasone (DEX), are known to demonstrate anti-inflammatory activity, suppress steroidogenesis, and mitigate the adverse effects of chemotherapy. They are therefore widely employed for managing solid malignancies. Emerging evidence indicates that DEX modulates both systemic and local renin–angiotensin system (RAS) activity, including genomic signaling via the glucocorticoid receptor (GR). Methods: DEX-dependent transcriptional responses for the angiotensin receptor genes (AGTR1, AGTR2, MAS1, and LNPEP) were evaluated in ovarian (SKOV3, KURAMOCHI) and prostate (DU-145, PC3) cancer cell lines. The cells were cultured under different serum conditions to determine the influence of nutrient availability on tumor progression. Results: DEX demonstrated distinct mechanisms of action between the ovarian and prostate cancer models. It was found to promote cancer cell survival through tissue-specific modulation of metabolic activity, clonogenic capacity, cell cycle distribution, and apoptotic responses. These effects were accompanied by condition-dependent alterations in angiotensin receptor gene expression. Hence, DEX may mediate the remodeling of local RAS signaling, which may be significant in overall survival and disease-free survival. The findings also indicate a previously-unreported NR3C1–LNPEP correlation, which was consistently observed across in vitro systems and patient datasets, in both ovarian- and prostate-derived cancer models. Conclusions: DEX appears to exert context-dependent regulation of RAS-associated gene networks in ovarian and prostate cancer, suggesting a role in tumor adaptive responses and potentially in therapeutic contexts. Full article

Background/Objectives: Elastin-derived peptides (EPs) from food sources may be multifunctional dietary components that support metabolic and vascular health. However, their in vivo physiological actions remain incompletely understood. This study investigated the effects of bonito bulbus arteriosus-derived EPs on glucose metabolism, GLP-1 elevation associated with enhanced early-phase insulin secretion, and renal vascular integrity in stroke-prone spontaneously hypertensive rats (SHRSP) with glucose intolerance. Methods: Male SHRSP were administered EPs orally as a single dose (1000 mg/kg) or 4-week regimen (600 mg/kg/day). Glucose tolerance, plasma GLP-1 and insulin levels, and blood glucose levels were measured following glucose loading. Renal morphology was assessed histologically. Dpp4, Icam-1, and Agtr1 expression was quantified in glomerular and leukocyte fractions. Leukocyte oxidative signaling was evaluated by quantifying reactive oxygen species production associated with inducible nitric oxide synthase (iNOS). Age-matched Wistar–Kyoto rats were included as normotensive controls. Results: A single dose increased plasma GLP-1 and insulin levels and improved glucose tolerance compared with controls. The 4-week regimen resulted in sustained improvements in glucose tolerance, without changes in blood pressure, a lower nephrosclerosis incidence, and reduced renal and leukocytic inflammatory marker expression. Dpp4, Icam-1, and Agtr1 expression was downregulated, and leukocyte iNOS-driven oxidative signaling was reduced. These effects occurred despite the modest DPP4 inhibitory activity of EPs. Conclusions: Food-derived EPs may exert multi-target physiological actions, including GLP-1 elevation with enhanced early-phase insulin secretion and leukocyte oxidative and inflammatory response suppression, which potentially improve metabolic and renal vascular outcomes. EPs warrant further exploratory investigation as candidate functional food ingredients for metabolic and vascular health. Full article

Background: The correlation between renal volume (or mass) and nephron number in newborns allows the use of the total kidney volume (TKV) at birth as a surrogate for congenital nephron number. Previously, the wide variation in final nephron number (termed “nephron endowment”) has been attributed to polymorphisms of genes encoding proteins involved in glomerulogenesis, including key genetic variants in the renin–angiotensin system. However, there are no data concerning the role of polymorphism in the gene encoding type-2 angiotensin II receptor (AGTR2) in the modulation of nephron endowment in humans. Therefore, the aim of our study was to analyze the possible association between AGTR2:rs1403543 polymorphism and kidney volume in Polish full-term healthy newborns. Methods: The study group consisted of 208 healthy, Polish, full-term newborns born to healthy women with uncomplicated pregnancies. The AGTR2:rs1403543 polymorphism was identified by PCR-RFLP in genomic DNA extracted from cord blood leukocytes. Kidney volume was measured sonographically. Total kidney volume was calculated as the sum of left and right kidneys, and normalized for body mass (BM), body length (BL), or body surface area (BSA). Results: There were no significant differences in TKV/BM, TKV/BL, or TKV/BSA between male and female newborns, as well as in regard to the AGTR2:rs1403543 polymorphism. Conclusions: The results suggest a lack of association between the AGTR2:rs1403543 polymorphism and physiological variability in kidney volume in full-term newborns. Full article

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), exploits angiotensin-converting enzyme 2 (ACE2) for cell entry, implicating the renin–angiotensin system (RAS) in disease pathogenesis. Hypertension (HT), a major comorbidity, is strongly influenced by genetic factors within RAS, including angiotensin ii receptor type 1 (AGTR1) and ACE2) polymorphisms. However, data on these variants in African populations remain scarce. This study investigated associations between AGTR1 and ACE2 single-nucleotide polymorphisms (SNPs), HT, and COVID-19 severity in patients at a Tshwane Academic Hospital. Methods: We genotyped AGTR1 and ACE2 SNPs in 94 PCR-confirmed COVID-19 patients using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) mass spectrometry. Clinical data were extracted from hospital records. Ordinal logistic regression models assessed relationships between SNPs, HT, and COVID-19 severity. Results: The cohort (mean age: 53.9 years; HT prevalence: 54.9%) exhibited mild (54.9%), moderate (18.6%), and severe (26.5%) COVID-19. Although the rs2106809 A genotype appeared to be associated with lower odds of severe disease (OR = 0.39, 95% CI: 0.14–1.08, p = 0.04), this observation should be interpreted with caution given the limited sample size of this study. Other SNPs and clinical variables showed no significant associations. Conclusions: This exploratory study represents the first description of AGTR1 and ACE2 SNP patterns in COVID-19 patients from Tshwane. While the rs2106809 variant may indicate a possible protective trend, the evidence remains preliminary. Age correlated with severity. Larger, multi-ethnic studies are needed to confirm these findings. Full article

Background/Objectives: Obesity is characterized by chronic low-grade inflammation, which plays a central role in the development of its metabolic complications. The genetic factors influencing this inflammatory phenotype remain incompletely understood. This study aimed to analyze the associations of functional polymorphisms in genes involved in extracellular matrix remodeling (MMP2, MMP9, MMP12, COL1A1), metabolism (MTHFR, CYP3A5), and vascular regulation (NOS3, AGTR1) with plasma cytokine profiles and to identify inflammatory subphenotypes in patients with obesity. Methods: The study included 127 individuals, comprising 73 patients with excess body weight (body mass index, BMI ≥ 25 kg/m²) and 54 individuals with normal weight (BMI 18.5–24.9 kg/m²). Genotyping of selected polymorphisms was performed using real-time PCR. Plasma concentrations of 47 cytokines and chemokines were measured by multiplex immunoassay. Results: Nominally significant associations between genetic variants and cytokine levels were identified. Polymorphisms COL1A1 rs1107946 (CA genotype) and MMP9 rs17576 (AG genotype) were associated with a favorable inflammatory profile (decreased IL-6 and increased IL-10, respectively). In contrast, the AGTR1 rs5186 (AC genotipe) variant was associated with elevated TNF-α, IP-10/CXCL10, while the MTHFR rs1801131 (AC genotipe) variant was linked to increased MIP-1β/CCL4, both reflecting a pro-inflammatory shift. Complex, pleiotropic associations were observed for MMP2 rs243865 (elevated IL-7 and Fractalkine/CX3CL1) and NOS3 rs1799983 (elevated MCP-1/CCL2 and Eotaxin/CCL11). Cluster analysis revealed distinct patient subpopulations with differing inflammatory signatures. In one well-defined subgroup, an exploratory model (test R² = 0.537) identified IL-8, IL-15, and albumin as candidate biomarkers predictive of BMI. Conclusions: The study identifies candidate genetic polymorphisms and inflammatory biomarkers associated with distinct patterns of systemic inflammation in obesity. These hypothesis-generating findings underscore the phenotypic heterogeneity of obesity and provide a basis for further research into the stratification of patients by the risk of developing metabolic complications. Full article

Endometrial cancers increase expression of the renin–angiotensin system (RAS). This study aimed to determine if inhibiting the RAS would reduce the viability and proliferation of endometrial cancer cells. The expression of RAS genes was measured in three endometrial epithelial adenocarcinoma cell lines (Ishikawa, HEC-1-A, AN3CA). Ishikawa cells had the highest expression of REN, ACE, and AGTR1 mRNA. AGT mRNA and protein levels were most abundant in HEC-1-A cells. We then determined the effects of drugs that inhibit the action of renin (VTP-27999 and aliskiren) or angiotensin-converting enzyme (perindoprilat) or block the angiotensin II type 1 receptor (losartan and telmisartan). Overall, VTP-27999, aliskiren, perindoprilat, and losartan had minimal effects on cell viability in all three cell lines, and combinations of these drugs did not have any effect. Telmisartan (a dual angiotensin receptor blocker and PPAR-γ agonist) significantly reduced the viability of all three cell lines and reduced the proliferation of both Ishikawa and AN3CA cells. Telmisartan was more effective than troglitazone (PPAR-γ agonist) in Ishikawa and HEC-1-A cells. RAS inhibitors were most effective in Ishikawa cells, which had the highest levels of RAS expression. Therefore, levels of RAS expression in endometrial cancers might indicate the potential efficacy of RAS drugs. Full article

Athletic performance results from complex interactions between genetic and environmental factors. This review compiles and synthesizes available literature on polymorphic genes associated with endurance, power, and strength performance, as well as their links to injury susceptibility and chronic metabolic diseases. Endurance performance is modulated by ACE, PPARGC1A, HFE, UCP2, UCP3, CDKN1A, and PPARA, regulating mitochondrial biogenesis, oxygen utilization, and muscle fiber composition. Power performance involves ACTN3, MCT1, IGF1, AMPD1, AGT, and AGTR2, affecting anaerobic metabolism, lactate clearance, and fast-twitch fiber recruitment. Strength performance is influenced by AR, PPARG, ARK2N, MMS22L, LRPPRC, PHACTR1, and MTHFR, related to androgen signaling, muscle hypertrophy, and recovery. Injury-related genes (COL1A1, COL5A1, IL6, VEGFA, NOG) and metabolic risk genes (FTO, PPARG, ADRB3) further highlight the clinical relevance of genomics. Collectively, these insights support the application of genetic information to personalize training, enhance performance, prevent injuries, and guide exercise interventions to mitigate metabolic disease risk. Full article

The venom of Nemopilema nomurai jellyfish represents a promising source of bioactive compounds with potential pharmacological applications. In our previous work, we identified two novel angiotensin-converting enzyme (ACE)-inhibitory peptides—IVGRPLANG (896.48 Da) and IGDEPRHQYL (1227.65 Da)—isolated from N. nomurai venom hydrolysates via papain digestion. In this study, we conducted a detailed biochemical and computational characterization of these peptides. The IC₅₀ values were determined to be 23.81 µM for IVGRPLANG and 5.68 µM for IGDEPRHQYL. Kinetic analysis using Lineweaver–Burk plots revealed that both peptides act as competitive ACE inhibitors, with calculated inhibition constants (K_i) of 51.38 µM and 5.45 µM, respectively. To assess the structural stability of the ACE–peptide complexes, molecular dynamics simulations were performed. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses provided insights into complex stability, while interaction fraction analysis elucidated key bond types and residue–ligand contacts involved in binding. Furthermore, a network pharmacology approach was employed to predict therapeutic targets within the renin–angiotensin–aldosterone system (RAAS). Eleven target proteins were identified: IVGRPLANG was associated with REN, ACE, CTSB, CTSS, and AGTR2; IGDEPRHQYL was linked to REN, AGT, AGTR1, AGTR2, KNG1, and BDKR2. Molecular docking analyses using HADDOCK software (version 2.4) were conducted for all targets to evaluate binding affinities, providing further insight into the peptides’ therapeutic potential. Full article

Background/Objectives: Left ventricular hypertrophy is a significant independent risk factor for increased cardiovascular morbidity and mortality. There are some reports indicating an association of rs1403543 (1675G>A) polymorphism in the AGTR2 gene, which encodes the type-2 angiotensin II receptor, with left ventricular hypertrophy or increased left ventricular mass (LVM) in adults. The aim of this study was to analyze the possible association of the AGTR2:rs1403543 polymorphism with LVM in full-term Polish healthy newborns. Methods: The study group comprised 207 consecutive, full-term, healthy newborns. LVM was assessed, on the 3rd day after birth, from the M-mode echocardiographic measurements of left ventricular dimensions using the Penn convention, with the Huwez et al.-modified equation mode. The AGTR2 polymorphism was identified by PCR-RFLP in genomic DNA extracted from cord blood leukocytes. Results: There were no significant differences in clinical and echocardiographic characteristics of male newborns in regard to the AGTR2:rs1403543 polymorphism. However, the LVM/body mass ratio in female newborns carrying at least one A allele (i.e., with genotype GA or AA) was significantly lower as compared to its value in reference (GG) homozygotes. In addition, in female newborns, the frequency of AGTR2 genotypes with at least one A allele was significantly higher in the lower tertile of LVM/body mass or LVM/body surface area (calculated using the Mosteller formula) ratios as compared with upper tertiles. Conclusions: Our results suggest that the AGTR2:rs1403543 polymorphism may be associated with the physiological variability of cardiac mass in female newborns. Full article

Objectives: This study aims to show the distribution of angiotensin-converting enzyme (ACE) rs1799752 (I>D) gene insertion/deletion (I/D) polymorphism and angiotensin II receptor type 1 (AGTR1) rs5186 (A>C) gene polymorphism in adolescents with hypertension (HT) and type 1 diabetes (T1D), as well as its association with hypertension and the diurnal variation of mean blood pressure (dipping phenomenon). Methods: A cross-sectional study was conducted involving 118 adolescents diagnosed with T1D who underwent clinical and laboratory investigations, genetic analyses, and 24 h ambulatory blood pressure monitoring. The genotype frequencies were compared between adolescents with HT and those with normal blood pressure. Additionally, the genotype frequencies were compared between dippers and non-dippers. Results: Patients with HT were more likely to be female and exhibited significantly poorer glycemic control and higher triglycerides, along with increased body mass index and daily insulin dosage. The prevalence of ACE rs1799752 genotypes in the hypertensive group was 20% II, 66.7% ID, and 13.3% DD, which did not significantly differ from the normal blood pressure group with 29.1% II, 53.4% ID, and 17.5% DD (p = 0.625). The prevalence of AGTR1 rs5186 genotypes in the hypertensive group was 53.3% AC, 40% AA, and 6.7% CC, which also did not significantly differ from the normal blood pressure group with 39.8% AC, 52.4% AA, and 7.8% CC (p = 0.608). A total of 46% of the patients exhibited non-dipping phenomena. The prevalence of non-dippers among the ACE genotypes was 13% DD, 33.3% II, and 53.7% ID (p = 0.369), while for the AGTR1 genotypes, it was 50% AA, 42.6% AC, and 7.4% CC (p = 0.976). Conclusions: Our results indicate that in our adolescents with T1D, clinical and metabolic factors such as higher body mass index, triglycerides, suboptimal glycemic control, and female gender are more indicative of the development of hypertension than ACE and AGTR1 gene polymorphisms. A potential reason for this finding could be the young age of the patients or the relatively small size of the study group. Future research involving larger sample sizes is needed to further investigate the genetic predisposition for the development of hypertension. Full article

Every individual at some point encounters the progressive biological process of aging, which is considered one of the major risk factors for common diseases. The main drivers of aging are oxidative stress, senescence, and reactive oxygen species (ROS). The renin–angiotensin–aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure, which is caused by an imbalance of electrolytes. During activation of the RAAS, binding of angiotensin II (ANG II) to angiotensin II type 1 receptor (AGTR1) activates intracellular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate superoxide anions and promote uncoupling of endothelial nitric oxide (NO) synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show downregulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase sirtuin-1 (SIRT1) has a significant impact on the aging process, with reduced activity with age. However, GS/BS patients generally sustain higher levels of sirtuin-1 (SIRT1) activity than age-matched healthy individuals. SIRT1 expression in GS/BS patients tends to be higher than in healthy age-matched individuals; therefore, it can be assumed that there will be a trend towards healthy aging in these patients. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose future research directions for studying the etiology of GS/BS at the molecular level using patient-derived renal stem cells and induced pluripotent stem cells. Full article

The objectives of this study were to explore the role that eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) plays in heart failure (HF), highlighting the potential connection to oxidative stress pathways. Following PRISMA guidelines, we conducted electronic searches of the literature in MEDLINE and EMBASE focusing on serum EPA and/or DHA and EPA and/or DHA supplementation in adult patients with heart failure or who had heart failure as an outcome of this study. We screened 254 studies, encompassing RCTs, observational studies, and cohort studies that examined HF outcomes in relation to either serum concentrations or dietary supplementation of EPA and/or DHA. The exclusion criteria were pediatric patients, non-HF studies, abstracts, editorials, case reports, and reviews. Eleven studies met our criteria. In meta-analyses, high serum concentrations of DHA were associated with a lower rate of heart failure with a hazard ratio of 0.74 (CI = 0.59–0.94). High serum concentrations of EPA also were associated with an overall reduction in major adverse cardiovascular events with a hazard ratio of 0.60 (CI = 0.46–0.77). EPA and DHA, or n3-PUFA administration, were associated with an increased LVEF with a mean difference of 1.55 (CI = 0.07–3.03)%. A potential explanation for these findings is the ability of EPA and DHA to inhibit pathways by which oxidative stress damages the heart or impairs cardiac systolic or diastolic function producing heart failure. Specifically, EPA may lower oxidative stress within the heart by reducing the concentration of reactive oxygen species (ROS) within cardiac tissue by (i) upregulating nuclear factor erythroid 2-related factor 2 (Nrf2), which increases the expression of antioxidant enzyme activity, including heme oxygenase-1, thioredoxin reductase 1, ferritin light chain, ferritin heavy chain, and manganese superoxide dismutase (SOD), (ii) increasing the expression of copper–zinc superoxide dismutase (MnSOD) and glutathione peroxidase, (iii) targeting Free Fatty Acid Receptor 4 (Ffar4), (iv) upregulating expression of heme-oxygenase-1, (v) lowering arachidonic acid levels, and (vi) inhibiting the RhoA/ROCK signaling pathway. DHA may lower oxidative stress within the heart by (i) reducing levels of mitochondrial-fission-related protein DRP-1(ser-63), (ii) promoting the incorporation of cardiolipin within the mitochondrial membrane, (iii) reducing myocardial fibrosis, which leads to diastolic heart failure, (iv) reducing the expression of genes such as Appa, Myh7, and Agtr1α, and (v) reducing inflammatory cytokines such as IL-6, TNF-α. In conclusion, EPA and/or DHA have the potential to improve heart failure, perhaps mediated by their ability to modulate oxidative stress. Full article

Coronary artery disease (CAD) is the leading cause of death in India. Many genetic polymorphisms play a role in regulating oxidative stress, blood pressure and lipid metabolism, contributing to the pathophysiology of CAD. This study examined the association between ten polymorphisms and CAD in the Jat Sikh population from Northern India, also considering polygenic risk scores. This study included 177 CAD cases and 175 healthy controls. The genetic information of GSTM1 (rs366631), GSTT1 (rs17856199), ACE (rs4646994), AGT M235T (rs699), AGT T174M (rs4762), AGTR1 A1166C (rs5186), APOA5 (rs3135506), APOC3 (rs5128), APOE (rs7412) and APOE (rs429358) and clinical information was collated. Statistical analyses were performed using SPSS version 27.0 and SNPstats. Significant independent associations were found for GST*M1, GST*T1, ACE, AGT M235T, AGT T174M, AGTR1 A1166C and APOA5 polymorphisms and CAD risk (all p < 0.05). The AGT CT haplotype was significantly associated with a higher CAD risk, even after controlling for covariates (adjusted OR = 3.93, 95% CI [2.39–6.48], p < 0.0001). The APOA5/C3 CC haplotype was also significantly associated with CAD (adjusted OR = 1.86, 95% CI [1.14–3.03], p < 0.05). A higher polygenic risk score was associated with increased CAD risk (adjusted OR = 1.98, 95% CI [1.68–2.34], p < 0.001). Seven polymorphisms were independently associated with an increase in the risk of CAD in this North Indian population. A considerable risk association of AGT, APOA5/C3 haplotypes and higher genetic risk scores is documented, which may have implications for clinical and public health applications. Full article