APOB gene polymorphisms are considered risk factors for the development of dyslipidemia, hypertension, and cardiovascular disease (CVD) in several populations. In Mexico, these pathologies are frequent and studies regarding this gene are scarce. The aim of this cross-sectional study was to determined genotype, allele, and haplotype frequencies of APOB polymorphisms and performed analyses of association among the biochemical, hemodynamic, anthropometrical, and genetic variables. Blood samples were taken from 361 subjects from unselected Mexican population for biochemical analysis and for deoxyribonucleic acid extraction; besides blood pressure and body mass index (BMI) were measured. APOB polymorphisms rs934197, rs533617, rs693, and rs1042031 were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism; whereas, rs17240441 and c.66_67insCTGCTG were genotyped by PCR followed by electrophoresis. Genotype and allele frequencies were obtained by simple counting and deviations from Hardy-Weinberg equilibrium (HWE) were calculated by chi-square test. The effect of the polymorphisms on the quantitative variables was determined using analysis of variance, Student's t test, Pearson's and Spearman's correlations and multiple linear regression models. All the polymorphisms were within HWE. Frequencies of mutated alleles were highly heterogeneous: rs934197-T 33.6%, rs17240441-D 39.3%, c.66_67insCTGCTG-I 3.9%, rs533617-G 0.9%, rs693-T 40.5%, and rs1042031-G 17.3%. Chronic degenerative diseases were frequent in the studied population: overweight-obesity 55.1%, dyslipidemia 45.8%, and hypertension 23.5%. The association analyses showed that despite adjustments for age and sex the mutated alleles rs934197-T, rs1042031G, c.66_67-insCTGCTG-I, and rs533617-G, were related to lower values of BMI, total cholesterol (TC), systolic blood pressure, and diastolic blood pressure, respectively. All polymorphisms analyzed except rs533517 and c.66_67insCTGCTG showed high frequencies of the mutated allele, making them useful for association studies. Our results revealed that, APOB gene polymorphisms could be contributing to the development of several chronic diseases, such as essential hypertension, dyslipidemias, obesity, among others. However, specific studies with each pathology are needed to know the possible implications of the polymorphisms.