Effects of familial hypercholesterolemia-associated genes on the phenotype of premature myocardial infarction

Lee, Chongyou; Cui, Yuxia; Song, Junxian; Li, Sufang; Zhang, Feng; Wu, Mingxin; Li, Long; Hu, Dan; Hong, Chen

doi:10.1186/s12944-019-1042-3

Cited by 8 publications

(6 citation statements)

References 23 publications

(22 reference statements)

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“…In case 3, the patient had a PCSK9 missense c.277C>T mutation on p.Arg93Cys (rs151193009). There are conflicting findings whether this particular mutation is pathogenic, a variant of uncertain significance, or benign [ 28 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

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Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care

et al. 2023

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Objective:Rare disease Background:In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. Case Reports:In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing. Conclusions:This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.

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Section: Discussionmentioning

confidence: 99%

“…The analysis of this patient showed a missense c.277C>T mutation in the PCSK9 gene (rs151193009), which was located within exon 2. There are conflicting findings whether this particular mutation is pathogenic, a variant of uncertain significance, or benign [28][29][30][31].…”

Section: Casementioning

confidence: 99%

Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care

et al. 2023

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“…Genetics play a critical role in the progression of PMI, with a heritability of 63% [ 6 ]. Additional evidence reveals that proprotein convertase subtilisin/kexin type 9 (Pcsk9) relates to cholesterol homeostasis, is a risk factor for PMI [ 7 – 9 ]. As a relatively new PMI risk factor, Pcsk9 has received widespread attention for elevating plasma low-density lipoprotein cholesterol levels due to promote degradation of LDL receptor in the liver [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction

et al. 2021

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Background Proprotein convertase subtilisin/kexin type 9 (Pcsk9) correlated with incidence and prognosis of coronary heart disease. However, it is unclear whether Pcsk9 contributed to coronary artery lesion severity in patients with premature myocardial infarction (PMI). The present study investigated associations between Pcsk9 and coronary artery lesion severity in PMI patients who underwent coronary angiography (CAG). Methods This prospective cohort study included young men (age ≤ 45 years, n = 332) with acute MI who underwent CAG between January 2017 and July 2019. Serum Pcsk9 levels and clinical characteristics were evaluated. SYNTAX scores (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) were calculated to quantify coronary artery lesions. Results Serum Pcsk9 levels were positively associated with SYNTAX scores (r = 0.173, P < 0.05). The diagnostic cutoff value of PSCK9 level was 122.9 ng/mL, yielding an area under the curve (AUC) of 0.63, sensitivity 81%, and specificity 40%. Serum Pcsk9, LDL-C, Apob, NT-proBnp, CK level, and diabetes history were independent predictors of high SYNTAX scores (P < 0.05). After stratifying by serum LDL-C level (cutoff = 2.6 mmol/L), medium-high Pcsk9 levels had increased risk of high SYNTAX scores in patients with high LDL-C (P < 0.05), and higher serum Pcsk9 levels had increased risk of major adverse cardiac events (MACE) after adjusting for confounding factors (P < 0.05). Conclusion Serum Pcsk9 levels correlates with severity of coronary artery lesion in PMI patients and may serve as a biomarker for severity of coronary artery stenosis in this patient population, which may contribute to risk stratification.

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“…PA is also a protective factor for the incidence of MI (18), although another study indicated that PA is not significantly associated with the risk of acute MI (19). Family history of premature coronary artery disease plays an important role in the development of MI (10). Many studies showed that identifying individuals with an increased risk of MI is a major challenge for enhancing prevention.…”

Section: Introductionmentioning

confidence: 99%

MIRKB: a myocardial infarction risk knowledge base

Zhan

Shi

et al. 2019

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Myocardial infarction (MI) is a common cardiovascular disease and a leading cause of death worldwide. The etiology of MI is complicated and not completely understood. Many risk factors are reported important for the development of MI, including lifestyle factors, environmental factors, psychosocial factors, genetic factors, etc. Identifying individuals with an increased risk of MI is urgent and a major challenge for improving prevention. The MI risk knowledge base (MIRKB) is developed for facilitating MI research and prevention. The goal of MIRKB is to collect risk factors and models related to MI to increase the efficiency of systems biological level understanding of the disease. MIRKB contains 8436 entries collected from 4366 articles in PubMed before 5 July 2019 with 7902 entries for 1847 single factors, 195 entries for 157 combined factors and 339 entries for 174 risk models. The single factors are classified into the following five categories based on their characteristics: molecular factor (2356 entries, 649 factors), imaging (821 entries, 252 factors), physiological factor (1566 entries, 219 factors), clinical factor (2523 entries, 561 factors), environmental factor (46 entries, 26 factors), lifestyle factor (306 entries, 65 factors) and psychosocial factor (284 entries, 75 factors). MIRKB will be helpful to the future systems level unraveling of the complex mechanism of MI genesis and progression.

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Effects of familial hypercholesterolemia-associated genes on the phenotype of premature myocardial infarction

Cited by 8 publications

References 23 publications

Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care

Case Series of Genetically Confirmed Index Cases of Familial Hypercholesterolemia in Primary Care

Pcsk9 is associated with severity of coronary artery lesions in male patients with premature myocardial infarction

MIRKB: a myocardial infarction risk knowledge base

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