Sequence analysis of the coding regions of the apolipoprotein C2 (APOC2) gene in Miniature Schnauzers with idiopathic hypertriglyceridemia

Xenoulis, Panagiotis G.; Tate, Nicole M.; Bishop, Micah A.; Steiner, Jörg M.; Suchodolski, Jan S.; Furrow, Eva

doi:10.1016/j.tvjl.2020.105559

Cited by 5 publications

(8 citation statements)

References 17 publications

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“…It was suggested that Schnauzer hyperlipidemia could be due to APOC2 deficiency, however Xenoulis et al [ 27 ] have not found coding variants in the APOC2 gene and concluded that APOC2 hereditary deficiency is unlikely to be a major cause for primary hyperlipidemia in this breed.…”

Section: Discussionmentioning

confidence: 99%

“…Possible mechanisms include increased production or reduced clearance of VLDL and chylomicrons or both [ 8 , 9 ]. Similarly, there is a familial hypertriglyceridaemia in humans, characterized by an increase in the production of VLDL [ 21 , 26 ] and apolipoprotein C-II (APOC2) deficiency, in humans is a very rare cause of hyperkylomycinemia, the most common cause is deficiency of lipoprotein lipase (LPL) [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

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Supplementation of omega-3 and dietary factors can influence the cholesterolemia and triglyceridemia in hyperlipidemic Schnauzer dogs: A preliminary report

et al. 2021

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Primary hyperlipidaemia in Schnauzer is characterized by increased plasma triglycerides (TG) and/or total cholesterol (TC) concentration and is associated with an increased risk of developing pancreatitis, insulin resistance and seizures. In humans, omega-3 fatty acids in addition to a low-fat diet can be used to reduce TG and TC. This study evaluated the therapeutic efficacy of omega-3 fatty acids associated to a diet management with two different fat content in Schnauzer with primary hyperlipidaemia. Eighteen dogs with primary hyperlipidaemia were divided into two groups: group 1, n = 10, 8 females, 2 males, age (mean ± standard deviation) of 7.13 ± 2.70 years and body weight (BW) (mean ± standard deviation) of 7.25 ± 1.22 kg were treated with fish oil (approximately 730 mg/day of omega-3) associated with a low-fat and low-calorie diet (approximately 24g of fat/1000 kcal) for 90 days (T90); and group 2, n = 8 dogs, 6 females, 2 males, with 7.0 ± 1.77 years old and average BW of 8.36 ± 1.51 kg, treated with fish oil (approximately 730 mg/day of omega-3) and maintenance diet with moderate amount of fat (approximately 33g of fat/1000 kcal) for 90 days. Plasma TG and TC concentrations and lipoprotein (LP) profile (VLDL, LDL, HDL) were evaluated before and after treatment. TG and TC serum concentrations, expressed in mg/dL (mean ± standard deviation), before and after treatment in group 1 were: TG = 391.30 ± 487.86 (T0) and 118.7 ± 135.21 (T90); TC = 308.2 ± 63.06 (T0) and 139 ± 36.91 (T90). As for group 2, TG = 391.63 ± 336.89 (T0) and 250.75 ± 211.56 (T90); TC = 257.25 ± 92.88 (T0) and 207.25 ± 63.79 (T90). A reduction (p<0.05) of TG and TC was observed in both groups. The distribution of TG and TC among LP was not different between the pre (T0) and post treatment (T90) periods. After 90 days of treatment, the administration of omega-3 fatty acids, associated with a low-fat or maintenance diet reduced triglyceridemia and cholesterolemia without altering LP profile. The current investigation shows that both therapies were effective in reducing plasma TC and TG concentrations without altering LP profile.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Supplementation of omega-3 and dietary factors can influence the cholesterolemia and triglyceridemia in hyperlipidemic Schnauzer dogs: A preliminary report

et al. 2021

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“…When HTG is present without an identifiable underlying cause, HTG is classified as primary. Primary HTG is believed to have a genetic origin in Miniature Schnauzers, though the contributing genetic risk factors are unresolved 12,13 …”

Section: Introductionmentioning

confidence: 99%

“…Primary HTG is believed to have a genetic origin in Miniature Schnauzers, though the contributing genetic risk factors are unresolved. 12 , 13…”

Section: Introductionmentioning

confidence: 99%

Clustering analysis of lipoprotein profiles to identify subtypes of hypertriglyceridemia in Miniature Schnauzers

Tate,

Yamkate,

Xenoulis

et al. 2024

Veterinary Internal Medicne

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BackgroundHypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, predisposing them to life‐threatening diseases. Varied responses to management strategies suggest the possibility of multiple subtypes.Hypothesis/ObjectiveTo identify and characterize HTG subtypes in Miniature Schnauzers through cluster analysis of lipoprotein profiles. We hypothesize that multiple phenotypes of primary HTG exist in this breed.AnimalsTwenty Miniature Schnauzers with normal serum triglyceride concentration (NTG), 25 with primary HTG, and 5 with secondary HTG.MethodsCross‐sectional study using archived samples. Lipoprotein profiles, generated using continuous lipoprotein density profiling, were clustered with hierarchical cluster analysis. Clinical data (age, sex, body condition score, and dietary fat content) was compared between clusters.ResultsSix clusters were identified. Dogs with primary HTG were dispersed among 4 clusters. One cluster showed the highest intensities for triglyceride‐rich lipoprotein (TRL) and low‐density lipoprotein (LDL) fractions and also included 4 dogs with secondary HTG. Two clusters had moderately high TRL fraction intensities and low‐to‐intermediate LDL intensities. The fourth cluster had high LDL but variable TRL fraction intensities with equal numbers of NTG and mild HTG dogs. The final 2 clusters comprised only NTG dogs with low TRL intensities and low‐to‐intermediate LDL intensities. The clusters did not appear to be driven by differences in the clinical data.Conclusions and Clinical ImportanceThe results of this study support a spectrum of lipoprotein phenotypes within Miniature Schnauzers that cannot be predicted by triglyceride concentration alone. Lipoprotein profiling might be useful to determine if subtypes have different origins, clinical consequences, and response to treatment.

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“…Previous studies have shown that the defects directly related to LPL gene variants are also relevant to the majority of severe hyperlipidemia cases (3)(4)(5)(6). The rest 5% are the results of variants in other genes involving in LPL functioning, including APOC2 (encoding apolipoprotein CII, activator of LPL; OMIM #207750) (7,8), APOA5 (encoding apolipoprotein AV, activator of LPL; OMIM #144650) (9,10), LMF1 (encoding lipase maturation factor 1, a tissue factor triggering the secretion of functional LPL and hepatic lipase; OMIM #611761) (11,12), and GPIHBP1 (encoding glycosylphosphatidylinositol-anchored highdensity lipoprotein-binding protein 1, the molecular platform by which LPL is able to interact with TG-rich lipoproteins, apolipoprotein CII, and apolipoprotein AV on the endothelial surface of capillaries; OMIM #612757) (13,14). Meanwhile, there are also other variants to be identified (3), and all these variants may result in LPL malfunction.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Successful Management of a 29-Day-Old Infant With Severe Hyperlipidemia From a Novel Homozygous Variant of GPIHBP1 Gene

et al. 2022

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BackgroundSevere hyperlipidemia is characterized by markedly elevated blood triglyceride levels and severe early-onset cardiovascular diseases, pancreatitis, pancreatic necrosis or persistent multiple organ failure if left untreated. It is a rare autosomal recessive metabolic disorder originated from the variants of lipoprotein lipase gene, and previous studies have demonstrated that most cases with severe hyperlipidemia are closely related to the variants of some key genes for lipolysis, such as LPL, APOC2, APOA5, LMF1, and GPIHBP1. Meanwhile, other unidentified causes also exist and are equally worthy of attention.MethodsThe 29-day-old infant was diagnosed with severe hyperlipidemia, registering a plasma triglyceride level as high as 25.46 mmol/L. Whole exome sequencing was conducted to explore the possible pathogenic gene variants for this patient.ResultsThe infant was put on a low-fat diet combined with pharmacological therapy, which was successful in restraining the level of serum triglyceride and total cholesterol to a low to medium range during the follow-ups. The patient was found to be a rare novel homozygous duplication variant-c.45_48dupGCGG (Pro17Alafs*22) in GPIHBP1 gene-leading to a frameshift which failed to form the canonical termination codon TGA. The mutant messenger RNA should presumably produce a peptide consisting of 16 amino acids at the N-terminus, with 21 novel amino acids on the heels of the wild-type protein.ConclusionsOur study expands on the spectrum of GPIHBP1 variants and contributes to a more comprehensive understanding of the genetic diagnosis, genetic counseling, and multimodality therapy of families with severe hyperlipidemia. Our experience gained in this study is also contributory to a deeper insight into severe hyperlipidemia and highlights the importance of molecular genetic tests.

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Sequence analysis of the coding regions of the apolipoprotein C2 (APOC2) gene in Miniature Schnauzers with idiopathic hypertriglyceridemia

Cited by 5 publications

References 17 publications

Supplementation of omega-3 and dietary factors can influence the cholesterolemia and triglyceridemia in hyperlipidemic Schnauzer dogs: A preliminary report

Supplementation of omega-3 and dietary factors can influence the cholesterolemia and triglyceridemia in hyperlipidemic Schnauzer dogs: A preliminary report

Clustering analysis of lipoprotein profiles to identify subtypes of hypertriglyceridemia in Miniature Schnauzers

Case Report: Successful Management of a 29-Day-Old Infant With Severe Hyperlipidemia From a Novel Homozygous Variant of GPIHBP1 Gene

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