Chronic liver disease, with viral or non-viral etiology, is endemic in many countries and is a growing burden in Asia. Among the Asian countries, Pakistan has the highest prevalence of chronic liver disease. Despite this, the genetic susceptibility to chronic liver disease in this country has not been investigated. We performed a comprehensive analysis of the most robustly associated common genetic variants influencing chronic liver disease in a cohort of individuals from Pakistan. A total of 587 subjects with chronic liver disease and 68 healthy control individuals were genotyped for the HSD17B13 rs7261356, MBOAT7 rs641738, GCKR rs1260326, PNPLA3 rs738409, TM6SF2 rs58542926 and PPP1R3B rs4841132 variants. The variants distribution between case and control group and their association with chronic liver disease were tested by chi-square and binary logistic analysis, respectively. We report for the first time that HSD17B13 variant results in a 50% reduced risk for chronic liver disease; while MBOAT7; GCKR and PNPLA3 variants increase this risk by more than 35% in Pakistani individuals. Our genetic analysis extends the protective role of the HSD17B13 variant against chronic liver disease and disease risk conferred by the MBOAT7; GCKR and PNPLA3 variants in the Pakistani population.

The world population is genetically predisposed to metabolic syndrome (MetS) and its components, also known as cardiometabolic risk phenotypes, which can cause severe health complications including coronary heart disease (CHD). Genetic variants in the 9p21 locus have been associated with CHD in a number of populations including Pakistan. However, the role of the 9p21 locus in MetS and cardiometabolic risk phenotypes (such as obesity, hypertension, hyperglycemia, and dyslipidemia) in populations with CHD or no established CHD has not been explored. Therefore, the present study was designed to explore the association of the minor/risk allele (C) of 9p21 locus SNP rs1333049 with MetS or its risk phenotypes regardless of an established CHD, in Pakistani subjects. Genotyping of rs1333049 (G/C) was performed on subjects under a case-control study design; healthy controls and cases, MetS with CHD (MetS-CHD⁺) and MetS with no CHD (MetS-CHD⁻), respectively. Genotype and allele frequencies were calculated in all study groups. Anthropometric and clinical variables (Means ± SD) were compared among study groups (i.e., controls, MetS + CHD and MetS-CHD) and minor/risk C allele carriers (GC + CC) vs. non-carriers (Normal GG genotype). Associations of the risk allele of rs1333049 SNP with disease and individual metabolic risk components were explored using adjusted multivariate logistic regression models (OR at 95% CI) with a threshold p-value of ≤0.05. Our results have shown that the minor allele frequency (MAF) was significantly high in the MAF cases (combined = 0.63, MetS-CHD⁺ = 0.57 and MetS-CHD⁻ = 0.57) compared with controls (MAF = 0.39). The rs1333049 SNP significantly increased the risk of MetS, irrespective of CHD (MetS-CHD⁺ OR = 2.36, p < 0.05 and MetS-CHD⁻ OR = 4.04, p < 0.05), and cardiometabolic risk phenotypes; general obesity, central obesity, hypertension, and dyslipidemia (OR = 1.56–3.25, p < 0.05) except hyperglycemia, which lacked any significant association (OR = 0.19, p = 0.29) in the present study group. The 9p21 genetic locus/rs1333049 SNP is strongly associated with, and can be a genetic predictor of, MetS and cardiometabolic risks, irrespective of cardiovascular diseases in the Pakistani population.

Background & Objectives: Apolipoproteins, specifically ApoA-I (a cardioprotective HDL component) and ApoB (associated with cardiovascular risk), are increasingly recognized for their value in diagnosing and predicting heart disease. This study focused on comparing these markers and the ApoB/ApoA-I ratio with traditional lipid profiles to assess their diagnostic and prognostic capabilities. Methods: In this cross-sectional study, 1,200 participants were categorized into three groups: control (n=250), training (n=450), and validation (n=500). Blood samples were analyzed for ApoB, ApoA-I, and conventional lipid profile. Advanced statistical methods, including logistic regression, ROC curve analyses, and propensity score matching, were applied to control for confounding factors and validate findings. Results: The training cohort showed significantly higher ApoB levels (1.20 ± 0.52 g/L) compared to controls (1.0 ± 0.40 g/L, p < 0.001), while ApoA-I levels were significantly lower (1.03 ± 0.34 g/L vs. 1.12 ± 0.34 g/L, p = 0.045). The ApoB/ApoA-I ratio was markedly elevated in the training group (1.46 ± 0.18) versus controls (1.06 ± 0.95, p < 0.001). ApoB proved to be the most reliable predictor of coronary artery disease with an AUC of 0.82, surpassing the ApoB/ApoA-I ratio (AUC 0.70) and ApoA-I (AUC 0.65). Cholesterol and triglycerides demonstrated weaker associations with CAD. Conclusion: ApoB and the ApoB/ ApoA-I ratio are superior markers for assessing CAD risk compared to traditional lipid profile. This investigation lends further support for incorporating apolipoprotein testing into clinical practice, enhancing CAD risk stratification, in particular for the high-risk population.

Cardiomyopathies, a leading cause of heart failure and mortality worldwide, are a diverse group of heart muscle disorders, with dilated cardiomyopathy being the most prevalent subtype. Numerous genetic variants, identified through GWAS and candidate gene studies, are associated with cardiomyopathies. This study aimed to evaluate the association of the rs10757278 SNP polymorphism on chromosome 9p21.3 near the CDKN2A and CDKN2B genes with cardiomyopathy, focusing on its role in genetic susceptibility to ischemic dilated cardiomyopathy. Methods: A case-control study was conducted with 200 participants (100 cardiomyopathy patients and 100 controls). Clinical and echocardiographic parameters were recorded, and genotyping was performed using tetra-arms PCR. Results: Statistical analysis revealed that rs10757278 was significantly associated with cardiomyopathy (Chi-sq=11.679, p=0.00291) in allelic and genotypic distributions. The GG genotype (p=0.00958) increased risk, identifying the G allele as the risk allele. For IDCM, significant associations were observed for GG and AG genotypes (p=0.02613, p=0.00104), with the G allele increasing risk (p=0.0031, OR=3.19, CI=1.51–7.17) and the A allele offering protection (p=0.00961, OR=0.35, CI=0.15–0.177). Conclusion: These findings highlight rs10757278 as a potential biomarker for cardiomyopathy risk profiling. Further large-scale studies are warranted to confirm these results and improve early diagnosis and genetic risk prediction for cardiomyopathies.

Objectives: This study aimed to evaluate the association of the rs10757278 single nucleotide polymorphism (SNP) with cardiomyopathy, particularly its role in genetic susceptibility to ischemic dilated cardiomyopathy (IDCM). Methodology: A case-control study was conducted including 200 participants—100 cardiomyopathy patients and 100 healthy controls. Clinical and echocardiographic parameters were systematically recorded. Genotyping for rs10757278 was performed using tetra-primer ARMS-PCR. Allele and genotype frequencies were analyzed with odds ratios, and Hardy-Weinberg equilibrium was assessed to determine genetic association. Results: Logistic regression analysis revealed a significant association of rs10757278 with cardiomyopathy (Chi-square = 11.679, p = 0.00291) in both allelic and genotypic distributions. The GG genotype (p = 0.00958) conferred an increased risk, with the G allele identified as the risk allele. Among cardiomyopathy subtypes, IDCM showed a significant association with rs10757278, particularly with the GG and AG genotypes (p = 0.02613 and p = 0.00104, respectively). Logistic regression indicated that the G allele substantially increased IDCM risk (p = 0.0031, OR = 3.19, 95% CI = 1.51–7.17), while the A allele appeared protective (p = 0.00961, OR = 0.35, 95% CI = 0.15–0.77). This SNP, a known genome-wide association study (GWAS) hit, is strongly linked to coronary artery disease (CAD) and ischemic dilated cardiomyopathy, highlighting its potential as a biomarker for cardiomyopathy risk stratification. Conclusion: The rs10757278 variant is significantly associated with cardiomyopathies, particularly ischemic dilated cardiomyopathy, in the Pakistani population. The G allele serves as a genetic predictor of disease susceptibility. Larger, multi-center studies are warranted to validate these findings and facilitate early diagnosis and genetic risk profiling for cardiomyopathies.