Diversity of Apolipoprotein E genetic polymorphism significance on cardiovascular risk is determined by the presence of Metabolic Syndrome among hypertensive patients

Abstract

BackgroundHypertension has a significant relevance as a cardiovascular risk factor. A consistent increase on world’s Metabolic Syndrome (MetS) incidence has been associated with an epidemic cardiovascular risk in different populations. Dislipidemia plays a major role determining the epidemic CV burden attributed to MetS. Apolipoprotein E (ApoE) is involved on cholesterol and triglycerides metabolism regulation. Once ApoE polymorphism may influence lipid metabolism, it is possible that it brings on individual susceptibility consequences for the development of MetS and cardiovascular risk. The objective of the study is to measure the discriminatory power of ApoE polymorphism in determining cardiovascular risk stratification based on the presence MetS in a cohort of hypertensive patients.MethodsIt was enrolled 383 patients, divided in two groups, classified by MetS presence (IDF criteria): Group 1: 266 patients with MetS (MetS +) and Group 2: 117 patients without Mets (MetS -). Patient’s data were collected by clinical evaluation, physical exam, file reviews and laboratory testing. Polymorphic ApoE analysis was performed by PCR amplification. Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards ApoE polymorphism. Mets CVD prevalence was analysed according to E4 allele prevalence.ResultsThe results evidenced 184 men (48%), 63,7% whites, 45,1% diabetics and 11,7% of patients were smokers. Mean age was 64,0 ± 12,0 years. When genotypic distribution was analyzed, E3/3 genotype and E3 allele frequencies were more prevalent. Among patients with MetS, we observed an independent association between CVD prevalence and E4 allele frequency (OR 2.42 (1.17- 5.0, p < 0,05)). On the opposite direction, in those without MetS, there was lesser CVD burden in E4 allele carriers (OR 0,14 (0,02-0,75)). These associations remained significant even after confounding factor corrections.ConclusionsThe results presented demonstrate that the association between ApoE gene and CVD may be modulated by the presence of MetS, with an increased CV burden observed among E4 allele carriers with the syndrome. On the opposite way, E4 allele carriers without visceral obesity had lesser prevalence of CVD.

Síndrome metabólica, aterosclerose e inflamação: tríade indissociável?

“…People who have three or more of the criteria listed above are considered to have the syndrome. 4,7,[11][12][13][14] It is possible to detect MS in people with normal BMI and so obesity can be defined as a risk factor, but is not present in all those with the syndrome.…”

Associação de variantes polimórficas com síndrome metabólica: uma revisão integrative

“…After filtering by availability and reading, consisting of reading the title, abstract, and keywords of each study, 15 articles were selected (Table 1). [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] the remainder were excluded from the analysis, because they were not aligned with the subject of the review or with the inclusion parameters.…”

“…The foci of identification of the studies selected were investigations of associations between a given genetic polymorphism of a gene involved in the process of a metabolic pathway and risk factors for MS, such as obesity, dyslipidemia, insulin resistance, and hypertension (Table 2). [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] The relationship between differences in the polymorphic frequency of genes involved in obesity and MS was analyzed in five studies with samples of adults and adolescents with different population profiles. One of them found that nutritional control and exercise may be more effective at preventing risks associated with MS in individuals with the A allele for polymorphism 48867A> C (Asp358Ala) IL6R (rs2228145).…”

“…31 Another investigation noted that the G allele of the IL6 SNP rs1800795 gene was associated with increased probability of MS and that the plasma fatty acid profile interacts with variants of the IL1B and IL10 genes to modulate manifestation of MS. 32 Another study with the ApoE polymorphism, involved in regulation of cholesterol and triglycerides metabolism found an association between the ApoE gene and the syndrome. 33 De Faria et al studied relationships between genes and hypertension, 34 but their analyses did not detect direct associations between patients with apparently treatment resistant hypertension and the leptin gene (LEP) or the leptin receptor gene (LEPR). Miranda et al 35 examined interactions between the eNOS gene and cardiovascular risk and their results suggested that while eNOS haplotypes were not relevant, the CC genotype of the T (786) C polymorphism is associated with MS in obese children and adolescents.…”

17-β-estradiol up-regulates apolipoprotein genes expression during osteoblast differentiation <i>in vitro </i>

“…The nature and function of the major apolipoproteins are summarized in Table 2. Apolipoproteins are physiologically important and are associated with different diseases (36)(37)(38), but their function has yet to be fully elucidated.…”