Anti-APOA5 (C-terminal) polyclonal antibody

Genetic variations in the APOA1/C3/A4/A5 gene cluster have been studied and proposed to be the leading key for susceptibility to cardiovascular diseases and age-associated disorders. We aimed to investigate the associations of rs12721026 (APOA1) and rs1729408 (APOA5) polymorphisms and their haplotypes with some age-related diseases, as well as with lipids and proteins serum levels in a cohort from a Brazilian Elderly Longitudinal Study (EPIDOSO). Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were carried out using logistic regression analysis, Student's t-test, and linkage disequilibrium (LD) analysis. Polymorphic allele frequencies were 0.095 and 0.449 for rs12721026 and rs1729408, respectively. The C-allele of rs1729408 was associated with higher high-density lipoprotein (HDL) (P = 0.022) and glycated hemoglobin levels (P = 0.020). We also showed that rs12721026 and rs1729408 were in LD. The GC haplotype, which is composed of the G-allele of rs12721026 and the C-allele of rs1729408, was significantly associated with obesity (P = 0.028), with higher glycated hemoglobin (P = 0.006), and fasting glucose (P = 0.0003) compared to the TT haplotype, which includes the wild-type alleles of both polymorphisms. Moreover, we found an association between the TC haplotype and higher HDL levels (P = 0.0039). This is the first time that haplotypes involving these polymorphisms were evaluated. Our results showed that these polymorphisms were involved in the development of obesity and in alterations of lipids and proteins serum levels in a Brazilian population. The present findings might also clarify the role of these polymorphisms and their haplotypes in lipids and proteins metabolism.

Background: Common variants of APOA5 gene affect plasma triglyceride (TG) in the population and a number of rare variants APOA5 have been reported in individuals with hypertriglyceridemia (HTG). Methods: APOA5 was analysed in 98 HTG individuals (plasma TG >9 mmol/L) in whom no mutations in LPL and APOC2 had been found. Results: Two patients were found to be heterozygous for two novel APOA5 variants. The first variant (p.L.253P) was identified in an obese male who consumed a diet rich in fat and simple sugars. He was also a carrier in trans of the common TG-raising p.S19W SNP (5*3 haplotype). The second variant (c.295-297 del GAG, p.E99 del) was found in a lean male with no life style or metabolic factors known to affect plasma TG. He was a carrier in trans of the TG-raising 5*2 haplotype and was homozygous for the rare c.1337 T allele of a SNP of GCKR gene. No mutations in other genes affecting plasma TG (LMF1 and GPIHBP1) were found in these patients. These APOA5 variants, resulted to be deleterious in silico, were not found in 350 control subjects. Conclusions: These novel APOA5 variants predispose to HTG in combination with other genetic or nutritional factors. (C) 2011 Elsevier B.V. All rights reserved.