Single Nucleotide Polymorphisms in Apolipoprotein B, Apolipoprotein E, and Methylenetetrahydrofolate Reductase Are Associated With Serum Lipid Levels in Northern Chilean Subjects. A Pilot Study

Abstract

Characterization of allelic variants is relevant to demonstrate associations among genetic background and susceptibility to develop cardiovascular diseases, which are the main cause of death in Chile. Association of APOB, APOE, and MTHFR polymorphisms with higher lipid levels and the risk of developing hypertension and cardiovascular diseases have been described. Thus, the aim of this study was to assess genotype distribution and relative allelic frequency of ApoB rs693, ApoE rs7412, ApoE rs429358, MTHFR rs1801131, and MTHFR rs1801133 allelic variants and their effects on lipid profile in young healthy men and women from Northern Chile. A group of 193 healthy subjects were enrolled for this study. Genotyping of rs693 (APOB), rs7412 and rs429358 (APOE), and rs1801131 and rs1801133 (MTHFR) polymorphisms were performed by real time PCR. In addition, lipid profiles were determined and associated to genetic data. The genotype distribution was APOB rs693 (CC = 37%, CT = 41%, and TT = 22%), APOE rs7412/rs429358 (E4 = 0.06, E3 = 0.91, and E2 = 0.03), MTHFR rs1801131 (AA = 57%, AC = 30%, and CC = 13%), and MTHFR rs1801133 (CC = 20%, CT = 47%, and TT = 33%). The association of the genetic variants with plasma lipid levels showed that women, but not men, carrying APOB mutated allele (T) and Apo E4 allele presented lower values of total cholesterol when compared with C/C homozygous genotype or E3 allele, respectively (p < 0.05). In addition, a subgroup analysis revealed that ApoB C/C homozygous women exhibited higher values of HDL-C when compared with men carrying identical genotype (p < 0.01). On the other hand, women carrying E4 allele exhibited lower values of triglycerides when compared with male carrying identical genotype (p < 0.05). Finally, women carrying mutate allele (C) for MTHFR rs1801131 showed lower levels of triglycerides when compared with A/A homozygous genotype (p < 0.05) and lower levels of LDL-C for MTHFR rs1801133 in females carrying (T) allele when compared with males carrying identical genotype (p < 0.05). In summary, the present data showed that APOB, APOE, and MTHFR single nucleotide polymorphisms are associated to lipid levels in a gender-dependent manner among healthy subjects from Northern Chile, especially in women.

Folate and Vitamin B12 Levels in Chilean Women with PCOS and Their Association with Metabolic Outcomes

“…A recent study determined both polymorphisms in a group of young, healthy men and women from northern Chile. In the case of the A1298C and C677T variants, the allele frequencies were similar in comparison to those observed in our population [49]. Additionally, a study conducted in a healthy Chilean mestizo population comprising 146 unrelated subjects, in which the C677T polymorphism was analyzed, showed the following allele frequencies: C = 0.52 and T = 0.48 [50], similar to our control group.…”

Association of CELSR2, APOB100, ABCG5/8, LDLR, and APOE polymorphisms and their genetic risks with lipids among the Thai subjects

“…In addition, the meta -analysis also supported that APOE4 allele increased the risk for hyperlipidemia in both Asians, and Caucasians populations ( Zhao et al 2021 ). In contrast, the APOE4 allele showed significantly lower concentrations of TC compared with APOE3 allele in women from Northern Chile ( Gálvez et al 2021 ). Moreover, APOE polymorphism was not found associated with serum lipids in Saudi populations ( Almigbal et al 2018 ).…”

Effect of Apolipoprotein E ε4 Allele on the Progression of Carotid Atherosclerosis Through Apolipoprotein Levels

“…Among three alleles, ε4 allele is associated with increased levels of total plasma cholesterol and LDL cholesterol levels, while ε2 allele was associated with the reverse effect. 6 …”