Haplotype analysis of the apolipoprotein A5 gene in obese pediatric patients

Horvatovich, Katalin; Bokor, Szilvia; Baráth, Ákos; Maász, Anita; Kisfali, Péter; Járomi, Luca; Polgár, Noémi; Tóth, Dénes; Répásy, Judit; Endreffy, E.; Molnár, Denés; Melegh, Béla

doi:10.3109/17477166.2010.490268

Cited by 23 publications

(19 citation statements)

References 45 publications

(56 reference statements)

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“…In consistent with our results, Horvatovich et al revealed that APOA5 *2 haplotype (containing the minor alleles of rs662799, rs2072560 and rs2266788) confers susceptibility to development of obesity in pediatric patients [13]. Additionally, in Aberle’s study, at baseline, TT homozygotes had a lower BMI compared to carriers of the C allele, although without a statistical significance [14].…”

Section: Discussionsupporting

confidence: 91%

Triglyceride-raising APOA5 genetic variants are associated with obesity and non-HDL-C in Chinese children and adolescents

et al. 2014

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BackgroundAlthough the association between the apolipoprotein A5 (APOA5) genetic variants and hypertriglyceridemia has been extensively studied, there have been few studies, particularly in children and adolescents, on the association between APOA5 genetic variants and obesity or non-high-density lipoprotein cholesterol (non-HDL-C) levels. The objective of this study was to examine whether APOA5 gene polymorphisms affect body mass index (BMI) or plasma non-HDL-C levels in Chinese child population.MethodsThis was a case–control study. Single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry for an association study in 569 obese or overweight and 194 healthy Chinese children and adolescents.ResultsGenotype distributions for all polymorphisms in both cohorts were in accordance with the Hardy-Weinberg distribution. The frequencies of the risk alleles in rs662799 and rs651821 SNPs in APOA5 gene were all increased in obese or overweight patients compared to the controls. After adjusted for age and sex, C carriers in rs662799 had a 1.496-fold [95% confidence interval (CI): 1.074-2.084, P = 0.017] higher risk for developing obesity or overweight than subjects with TT genotype, while C carriers in rs651821 had a 1.515-fold higher risk than subjects with TT genotype (95% CI: 1.088-2.100, P = 0.014). Triglyceride (TG) and non-HDL-C concentrations were significantly different among rs662799 variants and both were higher in carriers of minor allele than in noncarriers for TG (1.64 ± 0.96 vs. 1.33 ± 0.67 mmol/L) (P < 0.001), and for non-HDL-C (3.23 ± 0.92 vs. 3.02 ± 0.80 mmol/L) (P = 0.005), respectively. There was also a trend towards increased TG and non-high-density lipoprotein cholesterol levels for rs651821 C carriers (P < 0.001 and P = 0.002, respectively). Furthermore, to confirm the independence of the associations between APOA5 gene and TG or non-HDL-C levels, multiple linear regression analysis was performed and the relationships were not eliminated by adjustment for age, sex and BMI.ConclusionsThese findings suggest the TG-raising genetic variants in the APOA5 gene may influence the susceptibility of the individual to obesity, which may also contribute to an increased risk of high non-HDL-C levels in Chinese obese children and adolescents.

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Section: Discussionsupporting

confidence: 91%

Triglyceride-raising APOA5 genetic variants are associated with obesity and non-HDL-C in Chinese children and adolescents

et al. 2014

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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].…”

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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“…In another haplotype study [40], the major haplotype represented an independent protective effect against development of metabolic syndrome [31]. Tagging SNPs and the major haplotype profiles were compared in pediatric obese children with normal controls.…”

Section: Common Polymorphisms and Haplotypes Of Apoa5mentioning

confidence: 99%

Mutations of the Apolipoprotein A5 Gene with Inherited Hypertriglyceridaemia: Review of the Current Literature

Duga¹,

Sümegi²,

Kisfali³

et al. 2012

Current Medicinal Chemistry

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Apoliporotein A5 (APOA5), a member of the apolipoprotein family, plays a key regulatory role in triglyceride (TG) metabolism. Even though the exact biochemical background of its mechanism is not yet fully understood, diseases associated with this particular gene highlighted its key role in the metabolism of triglycerides in humans. Naturally occurring functional variants of the gene and their natural major haplotypes are known to associate with moderately elevated triglyceride levels, and are also known to confer risk or protection for major polygenic diseases, like coronary heart disease, stroke, or metabolic syndrome. On the other hand, case reports and even robust resequencing studies verified APOA5 mutations as underlying genetic defects behind extreme hypertriglyceridemic phenotype. Soon after the recognition of the first cases, there were indications which suggest the existence of less frequent genetic variants which, in combination with the common allelic variants of the gene, can define haplotypes that are associated with substantial triglyceride level increase. In addition, it became evident, that there are rare mutations of the APOA5 gene which can be associated with specific complex phenotypes and different types of hyperlipoproteinemia, which includes extremely high triglyceride levels with multiple organ pathology. These rare mutations may cause inheritable hypertriglyceridemia, but they presented at a low frequency and could not be captured by standard genotyping array screenings. The identification of new mutations still relies on the direct sequencing of APOA5 gene of patients with hypertriglyceridemia with an unusual pattern, individually or in huge resequencing studies.

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Haplotype analysis of the apolipoprotein A5 gene in obese pediatric patients

Abstract: While previous studies in adults demonstrated, that the APOA5 -1131C minor allele confers risk for adult metabolic syndrome, here we show, that the susceptibility nature of this SNP restricted to the APOA5*2 haplotype in pediatric obese subjects.

Cited by 23 publications

References 45 publications

Triglyceride-raising APOA5 genetic variants are associated with obesity and non-HDL-C in Chinese children and adolescents

Triglyceride-raising APOA5 genetic variants are associated with obesity and non-HDL-C in Chinese children and adolescents

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

Mutations of the Apolipoprotein A5 Gene with Inherited Hypertriglyceridaemia: Review of the Current Literature

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