<i>APOA1/A5</i>Variants and Haplotypes as a Risk Factor for Obesity and Better Lipid Profiles in a Brazilian Elderly Cohort

Chen, Elizabeth; Furuya, Tatiane Katsue; Mazzotti, Diego R.; Ota, Vanessa Kiyomi; Cendoroglo, Maysa Seabra; Ramos, Luiz Roberto; Araújo, Lara Quirino; Burbano, Rommel Rodrı́guez; Smith, Marı́lia de Arruda Cardoso

doi:10.1007/s11745-010-3426-z

Cited by 18 publications

(11 citation statements)

References 44 publications

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“…The Institutional Research Ethics Committee approved this study, and all participants or their representatives gave informed consent according to the Declaration of Helsinki. All clinical characterization of our sample, laboratory tests, and DNA extraction have been previously described (Chen et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

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Short Communication Association of APOA1 and APOA5 polymorphisms and haplotypes with lipid parameters in a Brazilian elderly cohort

Furuya

Chen²,

Ota³

et al. 2013

Genet. Mol. Res.

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ABSTRACT.Apolipoproteins have an important role in lipid metabolism and transport. Polymorphisms in the APOA1/C3/A4/ A5 gene cluster have been associated with lipid alterations and cardiovascular diseases. We investigated APOA1 XmnI, APOA5 S19W, and APOA5 -1131T>C polymorphisms in 377 individuals from a cohort of a longitudinal Brazilian elderly study. Allele frequencies, genotype distribution, and association with major morbidities as well as with lipids, creatinine, albumin, urea, glycated hemoglobin, and fasting glucose serum levels were investigated. Linkage disequilibrium and haplotype associations were also analyzed. This is the first time that haplotypes involving these polymorphisms were evaluated. Genotyping was performed by PCR-RFLP. Minor allele frequencies were 0.119, 0.071, and 0.158 for XmnI, S19W, and -1131T>C polymorphisms, respectively. We found a significant association of the -1131C allele with low LDL-C levels. We also observed that XmnI and S19W polymorphisms were in linkage disequilibrium. The C/G haplotype, which is composed of the wild-type allele of XmnI and the minor allele of S19W, was associated with high total cholesterol serum levels in this elderly population. We conclude that the -1131T>C polymorphism and the C/G haplotype, including XmnI and S19W polymorphisms, are associated with alterations in lipid levels and may be risk factors for cardiovascular disease in the Brazilian elderly.

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Section: Methodsmentioning

confidence: 99%

“…Linkage disequilibrium and haplotype association analyses were also performed. Details of the statistical analyses were described in our previous report (Chen et al, 2010).…”

Section: Methodsmentioning

confidence: 99%

Short Communication Association of APOA1 and APOA5 polymorphisms and haplotypes with lipid parameters in a Brazilian elderly cohort

Furuya

Chen²,

Ota³

et al. 2013

Genet. Mol. Res.

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“…In contrast to the −1131T>C (rs662799) variant the c533G>T variants or T1259C allele had lower BMI and reduced risk to obesity [52, 53]. The Brazilian elderly longitudinal study identified that the GC haplotype of polymorphisms in ApoA1 (rs12721026) and ApoA5 (rs1729408) were associated with high risk to obesity [54]. Similar associations were also observed in children with obesity (148 obese children and 46 with normal body weight) were more than 68% of the obese children were positive for S19W ApoA5 allele along with G-75A allele in ApoA1 [55].…”

Section: Apoa5 In Cardiometabolic Diseasesmentioning

confidence: 99%

The paradox of ApoA5 modulation of triglycerides: Evidence from clinical and basic research

Garelnabi

Lor

Jin

et al. 2013

Clinical Biochemistry

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Apolipoprotein A5 (ApoA5) is a key regulator of plasma triglycerides (TG), although its plasma concentration is very low compared to other known apoproteins. Over the years, researchers have attempted to elucidate the molecular mechanisms by which ApoA5 regulates plasma TG in vivo. Though still under debate, two theories broadly describe how ApoA5 modulates TG levels: (i) ApoA5 enhances the catabolism of TG-rich lipoproteins and (ii) it inhibits the rate of production of very low-density lipoprotein (VLDL), the major carrier of TGs. This review will summarize the basic and clinical studies that have attempted to describe the importance of ApoA5 in TG metabolism. Population studies conducted in various countries have demonstrated an association between single nucleotide polymorphisms (SNPs) in ApoA5 and the increased risk to cardiovascular disease and metabolic syndrome (including diabetes and obesity). ApoA5 is also highly expressed during liver regeneration and is an acute phase protein associated with HDL which was independent of its effects on TG metabolism. Conclusion Despite considerable evidences available from clinical and basic research studies, on the role of ApoA5 in TG metabolism and its indirect link to metabolic diseases, additional investigations are needed to understand the paradoxical role of this important apoprotein shown modulated by diet and from it polymorphism variants.

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“…Chen et al (2010) investigated the associations of APOA1 PstI and APOA5 −12238T>C polymorphisms and their haplotypes with obesity in a cohort from a Brazilian Elderly Longitudinal Study (EPIDOSO). Chen et al (2010) investigated the associations of APOA1 PstI and APOA5 −12238T>C polymorphisms and their haplotypes with obesity in a cohort from a Brazilian Elderly Longitudinal Study (EPIDOSO).…”

Section: Apoa5 Gene Polymorphisms and Association With Obesity Anmentioning

confidence: 99%

The role of apolipoprotein A5 in obesity and the metabolic syndrome

2012

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Apolipoprotein A5 (apoA5) has an important role in lipid metabolism, specifically for triglyceride-rich lipoproteins. Recently, evidence has emerged for an association between genetic variability at the APOA5 locus and increased risk of obesity and metabolic syndrome. However, its mechanism of action remains to be fully elucidated. Importantly, an intracellular role of apoA5 has been indicated since apoA5 is associated with cytoplasmic lipid droplets and affects intrahepatic triglyceride accumulation, as well as affecting intravascular triglyceride metabolism. Given that adipocytes provide the largest storage depot for energy in the form of triglyceride within the lipid droplets, and play a crucial role in the development of obesity, we highlight recent findings discussing the interaction of apoA5 with adipocytes or adipose tissue, indicating that apoA5 may act as a novel regulator to modulate triglyceride storage in adipocytes. We review the association of APOA5 gene polymorphisms with obesity and metabolic syndrome, and propose potential mechanisms by which apoA5 may increase susceptibility to these conditions. This review provides new insights into the physiological role of apoA5 and identifies a potential therapeutic target for obesity and associated disorders.

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APOA1/A5Variants and Haplotypes as a Risk Factor for Obesity and Better Lipid Profiles in a Brazilian Elderly Cohort

Cited by 18 publications

References 44 publications

Short Communication Association of APOA1 and APOA5 polymorphisms and haplotypes with lipid parameters in a Brazilian elderly cohort

Short Communication Association of APOA1 and APOA5 polymorphisms and haplotypes with lipid parameters in a Brazilian elderly cohort

The paradox of ApoA5 modulation of triglycerides: Evidence from clinical and basic research

The role of apolipoprotein A5 in obesity and the metabolic syndrome

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