Polymorphisms of apolipoprotein E in the Afro-descendant population of Buenaventura, Colombia.

OBJETIVES: To estimate the frequency distribution, both allelic and genotypic, of the APOE gene in the Afro-descendant population of Buenaventura, Colombia. METHODS: Three hundred and forty-eight Afro-descendant individuals were analysed and the APOE locus was genotyped by PCR-RFLP. The allelic and genotypic frequencies were established by direct counting and the Hardy-Weinberg equilibrium was evaluated through χ2 test. The frequencies obtained in this study were compared with frequencies reported for other Colombian populations through the Fisher's exact test. RESULTS: The following allelic frequencies were observed: E3, 70.8%; E4, 21.4%, and E2, 7.8%. The genotypic frequencies were: E3/E3, 51.1%; E3/E4, 27.3%; E2/E3, 12.1%; E4/E4, 6%; E2/E4, 3.5%, and E2/E2, 0%. The entire examined population was found in Hardy-Weinberg equilibrium (P=.074), and significant differences were found in the allele E4 when comparing this population with the Amerindian and mestizo populations of Bogotá, Quindío, Centro-Oriente, Valle del Cauca, Barranquilla and Medellín (P≤ 0.0345). CONCLUSIONS: The allelic frequencies observed in this study were significantly different from the frequencies reported in other Colombian populations. The high representativeness of the E4 and E2 alleles validates the hypothesis that there are micro-evolutionary processes that have been acting on their frequencies and could be associated with susceptibility to neuropsychiatric diseases such as Alzheimer's disease, metabolic alterations of fats and/or coronary artery disease.

Polymorphisms of apolipoprotein E in the Afro-descendant population of Buenaventura, Colombia / Polimorfismos del gen de la apopoliproteína E en la población afrodescendiente de Buenaventura, Colombia

ABSTRACT Objetives: To estimate the frequency distribution, both allelic and genotypic, of the APOE gene in the Afro-descendant population of Buenaventura, Colombia. Methods: Three hundred and forty-eight Afro-descendant individuals were analyzed and the APOE locus was genotyped by PCR-RFLP. The allelic and genotypic frequencies were established by direct counting and the Hardy-Weinberg equilibrium was evaluated through X2 test. The frequencies obtained in this study were compared with frequencies reported for other Colombian populations through the Fisher's exact test. Results: The following allelic frequencies were observed: E3, 70.8%; E4, 21.4%, and E2, 7.8%. The genotypic frequencies were: E3/E3, 51.1%; E3/E4, 27.3%; E2/E3, 12.1%; E4/E4, 6%; E2/E4, 3.5%, and E2/E2, 0%. The entire examined population was found in Hardy-Weinberg equilibrium (P = .074), and significant differences were found in the allele E4 when comparing this population with the Amerindian and mestizo populations of Bogotá, Quindío, Centro-Oriente, Valle del Cauca, Barranquilla and Medellín (P< 0.0345). Conclusions: The allelic frequencies observed in this study were significantly different from the frequencies reported in other Colombian populations. The high representativeness of the E4 and E2 alleles validates the hypothesis that there are micro-evolutionary processes that have been acting on their frequencies and could be associated with susceptibility to neuropsychiatric diseases such as Alzheimer's disease, metabolic alterations of fats and/or coronary artery disease.

RESUMEN Objetivos: Estimar la distribución de frecuencias tanto alélicas como genotípicas del gen APOE en la población afrodescendiente de Buenaventura, Colombia. Métodos: Mediante la técnica de PCR-RFLP's se analizaron 348 individuos no relacionados de esta ciudad. Se realizó el cálculo de frecuencias alélicas y genotípicas y se evaluó el equilibrio de Hardy-Weinberg mediante la prueba de la X2. Se compararon las frecuencias alélicas obtenidas en el presente estudio con otras poblaciones de Colombia mediante el test exacto de Fisher. Resultados: Se reportaron las siguientes frecuencias alélicas: E2, 7,8%; E3, 70,8%, y E4, 21,4%. Las frecuencias genotípicas fueron: E3/E3, 51,1%; E3/E4,27,3%; E4/E4,6%; E2/E3,12,1%; E2/E4, 3,5%, y E2/E2, 0%. La población total se encontró en equilibrio de Hardy-Weinberg (p = 0,074), y se hallaron diferencias significativas en el alelo E4 al comparar esta población con las amerindias y mestizas de Bogotá, Quindío, Centro-Oriente, Valle del Cauca, Barranquilla y Medellín (p < 0,0345). Conclusiones: Las frecuencias alélicas observadas fueron significativamente diferentes de las frecuencias reportadas en otras poblaciones de Colombia. La alta representatividad de los alelos E4 y E2 validan la hipótesis de que hay procesos microevolutivos que han venido actuando en sus frecuencias y pueden estar asociadas con susceptibilidad a enfermedades neuropsiquiátricas como la enfermedad de Alzheimer, alteraciones metabólicas de las grasas y/o enfermedad coronaria.

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

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.

Polymorphisms of apolipoprotein E in the Afro-descendant population of Buenaventura, Colombia.

OBJETIVES: To estimate the frequency distribution, both allelic and genotypic, of the APOE gene in the Afro-descendant population of Buenaventura, Colombia. METHODS: Three hundred and forty-eight Afro-descendant individuals were analysed and the APOE locus was genotyped by PCR-RFLP. The allelic and genotypic frequencies were established by direct counting and the Hardy-Weinberg equilibrium was evaluated through χ2 test. The frequencies obtained in this study were compared with frequencies reported for other Colombian populations through the Fisher's exact test. RESULTS: The following allelic frequencies were observed: E3, 70.8%; E4, 21.4%, and E2, 7.8%. The genotypic frequencies were: E3/E3, 51.1%; E3/E4, 27.3%; E2/E3, 12.1%; E4/E4, 6%; E2/E4, 3.5%, and E2/E2, 0%. The entire examined population was found in Hardy-Weinberg equilibrium (P=.074), and significant differences were found in the allele E4 when comparing this population with the Amerindian and mestizo populations of Bogotá, Quindío, Centro-Oriente, Valle del Cauca, Barranquilla and Medellín (P≤ 0.0345). CONCLUSIONS: The allelic frequencies observed in this study were significantly different from the frequencies reported in other Colombian populations. The high representativeness of the E4 and E2 alleles validates the hypothesis that there are micro-evolutionary processes that have been acting on their frequencies and could be associated with susceptibility to neuropsychiatric diseases such as Alzheimer's disease, metabolic alterations of fats and/or coronary artery disease.

Phytosterol containing diet increases plasma and whole body concentration of phytosterols in apoE-KO but not in LDLR-KO mice.

Phytosterol metabolism is unknown in the hypercholesterolemia of genetic origin. We investigated the metabolism of phytosterols in a cholesterol-free, phytosterol-containing standard diet in hypercholesterolemic mice knockouts for low density lipoprotein receptor (LDLR) and apolipoprotein E (apoE) mice compared to wild-type mice (controls). Phytosterols were measured in mice tissues by GCMS. ApoE-KO mice absorbed less phytosterols than LDLR-KO and the latter absorbed less phytosterols than control mice, because the intestinal campesterol content was low in both KO mice, and sitosterol was low in the intestine in apoE-KO mice as compared to LDLR-KO mice. Although the diet contained nine times more sitosterol than campesterol, the concentration of sitosterol was lower than that of campesterol in plasma in LDLR-KO, and in the liver in controls and in LDLR-KO, but only in apoE-KO. On the other hand, in the intestine sitosterol was higher than campesterol in controls, and in LDLR-KO but with a tendency only in apoE-KO. Because of the high dietary supply of sitosterol, sitosterol was better taken up by the intestine than campesterol, but the amount of sitosterol was lower than that of campesterol in the liver, while in the whole body the amounts of these phytosterols do not differ from each other. Therefore, via intestinal lymph less sitosterol than campesterol was transferred to the body. However, as compared to controls, in apoE-KO mice, but not in LDLR-KO mice, the increase in campesterol and sitosterol in plasma and in the whole body indicating that apoE-KO mice have a marked defect in the elimination of both phytosterols from the body.

Prevalence of seven cardiovascular-related genetic polymorphisms in a Chilean mestizo healthy population.

OBJECTIVE: Among the genetic factors associated with cardiovascular disease (CVD), determining polymorphic genotypes could help to understand the appearance of the illness. Ethnic differences in these polymorphisms could explain population variability in susceptibility to CVD. The main goal of this research is to study the presence of more relevant genetic variants of ApoE, CETP, ACE, PAI-1, MTHFR, FII and FVL of the coagulation cascade, to describe the presence of cardiovascular-related variants in a mestizo group of the Chilean people. METHODS AND RESULTS: The studied population comprised 146 unrelated subjects from the general population, diagnosed as healthy, who were genotyped through conventional and/or real-time PCR. The allele frequencies for the Chilean population were: Apo E, ε2: 0.036, ε3: 0.875 and ε4: 0.089; CETP, B1: 0.51 and B2: 0.49; MTHFR, C: 0.52 and T: 0.48; ACE, I: 0.603 and D: 0.397; PAI-1, 4G: 0.381 and 5G: 0.619; FII, G: 0.97 and A: 0.03, and FV Leiden, G: 0.97 and A: 0.03. CONCLUSIONS: This study contributes to establish a first picture in the Chilean mestizo population about the frequencies of these variants, which could act as single or complementary risk factors to trigger CVD. The obtained allele frequencies show great differences in relation to other South American populations.

Protective effect of the APOE-e3 allele in Alzheimer’s disease

Although several alleles of susceptibility to Alzheimer’s disease (AD) have been studied in the last decades, few polymorphisms have been considered as risk factors for the disease. Among them, the APOE-e4 allele appears to be the major genetic risk factor for the onset of the disease. However, it is important to confirm the potential susceptibility of these genetic variants in different populations in order to establish a genetic profile for the disease in specific communities. This study analyzed the APOE polymorphisms regarding susceptibility to AD in a sample of 264 individuals (primarily Caucasians; 82 cases and 182 controls) in the population from Vitória, ES, Brazil, by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The patients were selected according to clinical criteria for probable AD. Whereas the e4 allele showed statistically significant positive association with susceptibility to AD (OR = 3.01, 95 percentCI = 1.96-4.61; P < 0.0001), the e2 allele did not. The results of the e4 allele confirm the role of this polymorphism as a risk factor for AD in the sample studied as observed in other populations. Although the e3 allele has been considered neutral in several studies, our results suggest that it acts as a protective factor against AD in the population studied (OR = 0.46, 95 percentCI = 0.30-0.67; P < 0.0001). This study may provide a new insight into the role of the APOE-e3 allele in the etiology of AD and might help to estabilish a profile of risk for AD in the population from Vitória, ES.