9p21 Locus Polymorphism Is A Strong Predictor of Metabolic Syndrome and Cardiometabolic Risk Phenotypes Regardless of Coronary Heart Disease

• Published in: Genes Vol. 13; no. 12; p. 2226
• Main Authors: Mobeen Zafar, Muhammad, Saqlain, Muhammad, Mehmood Raja, Asad, Arzoo Shaiq, Pakeeza, Javaid Asad, Muhammad, Nawaz Shah, Muhammad Kausar, Fatima, Farah, Valadi, Hadi, Nawaz, Muhammad, Raja, Ghazala Kaukab
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.11.2022; MDPI
• Subjects: 9p21 locus; Age; Alleles; Analysis; Body mass index; cardiometabolic risk phenotype; Cardiovascular disease; Cardiovascular Diseases; Case-Control Studies; CHD; Chi-square test; Clinical Medicine; Coronary artery disease; Coronary Disease; Coronary Disease - epidemiology; Coronary Disease - genetics; Coronary heart disease; Development and progression; Dyslipidemia; epidemiology; Ethnicity; Gender; Gene frequency; Gene loci; Gene polymorphism; Genes; Genetic diversity; genetics; Genotype & phenotype; Genotyping; Health aspects; Health risk assessment; Health Sciences; Heart diseases; High density lipoprotein; Humans; Hyperglycemia; Hypertension; Hälsovetenskaper; Klinisk medicin; Medical Biotechnology; Medicinsk bioteknologi; Metabolic disorders; Metabolic Syndrome; Metabolic Syndrome - genetics; Metabolic syndrome X; Obesity; Phenotype; Phenotypes; Polymorphism; Polymorphism, Single Nucleotide; Population; Population genetics; Regression analysis; Single Nucleotide; Single-nucleotide polymorphism; Variance analysis; Pakistan; metabolic syndrome; coronary heart disease; 9p21 locus; CHD; obesity; cardiometabolic risk phenotype
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes13122226

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 -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, < 0.05 and MetS-CHD OR = 4.04, < 0.05), and cardiometabolic risk phenotypes; general obesity, central obesity, hypertension, and dyslipidemia (OR = 1.56-3.25, < 0.05) except hyperglycemia, which lacked any significant association (OR = 0.19, = 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.