A single nucleotide substitution in the promoter region of the apolipoprotein C-II gene identified in individuals with chylomicronemia

Streicher, Rüdiger; Geisel, J.; Weisshaar, C; Avci, Haluk; Oette, K.; Müller‐Wieland, Dirk; Krone, Wilhelm

doi:10.1016/s0022-2275(20)37463-0

Cited by 19 publications

(3 citation statements)

References 17 publications

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“…Apolipoprotein C-II deficiency in newborns can cause severe mental development problems secondary to lipid encephalopathy [67]. The majority of homozygous carriers of APOC2 variants arise in consanguinity kindreds [64,[68][69][70][71][72]. APOC2 variants include apoC-II Auckland (c.255C>A [p.Tyr85*]) [73], apoC-II Bari (c.177C>G [p.Tyr59*]) [74], apoC-II Colombia (c.133_134del [p.Ser45Glnfs*24]) [75], apoC-II Nijmegen (c.118del [p.Val40*]) [76], apoC-II Padova (c.177C>A [p.Tyr59*]) [68], apoC-II Shangai (c.86delinsCC [p.Asn29Alafs*2]) [77], apoC-II Toronto (c.270del [p.Asp69Thrfs*7]) [78], and apoC-II Paris2 (c.10C>T [p.Arg4*]) [79].…”

Section: Apolipoprotein C-iimentioning

confidence: 99%

“…ApoC-II Tuzla (g.17,719,326-17,722,303del) [70] occurs from a deletion, which covers the entire coding sequence corresponding to exons 2, 3 and 4. Concerning point variants within the promoter region, the A to G transition in the APOC2 proximal promoter (c.-25-90A>G) resulted in a substantially diminished binding of the complementary cis-regulatory element, and therefore compromises the transcription [72]. Similarly, T to A transversion at position -190 in the promoter region (c.-25-190T>A) also reduces the transcriptional activity [66].…”

Section: Apolipoprotein C-iimentioning

confidence: 99%

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Understanding Hypertriglyceridemia: Integrating Genetic Insights

Alves,

Laranjeira,

Correia-da-Silva

2024

Genes

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Hypertriglyceridemia is an exceptionally complex metabolic disorder characterized by elevated plasma triglycerides associated with an increased risk of acute pancreatitis and cardiovascular diseases such as coronary artery disease. Its phenotype expression is widely heterogeneous and heavily influenced by conditions as obesity, alcohol consumption, or metabolic syndromes. Looking into the genetic underpinnings of hypertriglyceridemia, this review focuses on the genetic variants in LPL, APOA5, APOC2, GPIHBP1 and LMF1 triglyceride-regulating genes reportedly associated with abnormal genetic transcription and the translation of proteins participating in triglyceride-rich lipoprotein metabolism. Hypertriglyceridemia resulting from such genetic abnormalities can be categorized as monogenic or polygenic. Monogenic hypertriglyceridemia, also known as familial chylomicronemia syndrome, is caused by homozygous or compound heterozygous pathogenic variants in the five canonical genes. Polygenic hypertriglyceridemia, also known as multifactorial chylomicronemia syndrome in extreme cases of hypertriglyceridemia, is caused by heterozygous pathogenic genetic variants with variable penetrance affecting the canonical genes, and a set of common non-pathogenic genetic variants (polymorphisms, using the former nomenclature) with well-established association with elevated triglyceride levels. We further address recent progress in triglyceride-lowering treatments. Understanding the genetic basis of hypertriglyceridemia opens new translational opportunities in the scope of genetic screening and the development of novel therapies.

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Section: Apolipoprotein C-iimentioning

confidence: 99%

Section: Apolipoprotein C-iimentioning

confidence: 99%

Understanding Hypertriglyceridemia: Integrating Genetic Insights

Alves,

Laranjeira,

Correia-da-Silva

2024

Genes

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“…Influenced by a number of cofactors, LPL plays a key role in both the exogenous and the endogenous lipid metabolism. ApoC2 serves as an activator of the enzyme [6][7][8], hence lack of apoC2 leads to a curbed LPL function. Lipase maturation factor-1 (LMF1) plays a role in the formation of the proper structure of LPL and regulates its expression [9].…”

Section: Factors Influencing Lipoprotein Lipase Activitymentioning

confidence: 99%

Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia

et al. 2022

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The prevalence of hypertriglyceridemia has been increasing worldwide. Attention is drawn to the fact that the frequency of a special hypertriglyceridemia entity, named chylomicronemia syndrome, is variable among its different forms. The monogenic form, termed familial chylomicronemia syndrome, is rare, occuring in 1 in every 1 million persons. On the other hand, the prevalence of the polygenic form of chylomicronemia syndrome is around 1:600. On the basis of the genetical alterations, other factors, such as obesity, alcohol consumption, uncontrolled diabetes mellitus and certain drugs may significantly contribute to the development of the multifactorial form. In this review, we aimed to highlight the recent findings about the clinical and laboratory features, differential diagnosis, as well as the epidemiology of the monogenic and polygenic forms of chylomicronemias. Regarding the therapy, differentiation between the two types of the chylomicronemia syndrome is essential, as well. Thus, proper treatment options of chylomicronemia and hypertriglyceridemia will be also summarized, emphasizing the newest therapeutic approaches, as novel agents may offer solution for the effective treatment of these conditions.

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