Gene–Diet Interactions
Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss in Nutrition and Cardiometabolic Health, 2017
Some pioneering studies in the field of gene–diet interactions and cardiometabolic health relate to candidate genes in the path of lipoprotein metabolism, specifically associated with the APOE and the APOA1/APOC3/APOA4/APOA5 gene cluster. However, whereas there are clear and consistent associations between some of these loci and plasma lipid concentrations, the results from gene–diet interactions suffer from the similar lack of replication found for other metabolic pathways.
Advances in diagnosis and potential therapeutic options for familial chylomicronemia syndrome
Published in Expert Opinion on Orphan Drugs, 2018
Lane B. Benes, Eric J. Brandt, Michael H. Davidson
A single point mutation of one APOA5 allele without other significant gene variants was of surprise given the extent of his hypertriglyceridemia and symptoms. He exhibited an FCS phenotype despite normal thyroid function tests, regular physical activity, and lack of medication administration known to raise TG. He was obese with a body mass index of 35 and was suspected to have insulin resistance in addition to his decreased insulin production due to pancreatic insufficiency. Initially he had adequate control of his diabetes; however, his hemoglobin A1c eventually rose to the 9–10% range. It is felt that his FCS phenotype is out of proportion to his genotype; his case exemplifies polygenic FCS that is due to partial loss of LPL activity along with other causes of hypertriglyceridemia such as extreme insulin resistance and likely other genetic variants that are unaccounted for in the current five-gene testing approach. He reported adequate dietary adherence; however, it is conceivable that there was suboptimal adherence given the demanding diet constraints of the optimal FCS diet.
Treatment of hypertriglyceridemia-induced acute pancreatitis with therapeutic plasma exchange in 2 pregnant patients
Published in Journal of Obstetrics and Gynaecology, 2019
Altay Kandemir, Adil Coşkun
A 37-year-old primiparous woman was admitted to the gastroenterology department of our hospital with complaints of epigastric pain and nausea during her 22nd week of gestation. She had an attack history of having HTG-AP, 3 years before this attack. In the medical history, there was an uncontrolled hypertriglyceridaemia with an irregular usage of fenofibrate for 10 years. The fibrate treatment was stopped due to her pregnancy. The patient’s weight was 63 kg, and her height was 162 cm. On physical examination, her arterial blood pressure was 105/60 mmHg, heart rate was 85/min, blood temperature was 37.0 °C. A physical examination revealed a rebound tenderness on epigastrium. The laboratory results are shown in Table 1. As a result of a sequence analysis, testing for APOA5 (apolipoprotein A5) ve LIPI (LIPASE I) genetic mutation associated with hypertriglyceridaemia were negative. The results of arterial blood gas analysis were pH: 7.40, PCO2: 33.8 mmHg, PO2: 41.5 mmHg, HCO3: 22.9 mmol/L, SO2: 77.2%. The Ranson’s score was 2 at admission and at the 48th hour. We stopped the oral intake and administered an analgesic and serum saline (4–6 L/day) therapy. Haemonetics MCS+ (Haemonetics Corp. Braintree, USA) was used in TPE procedures. Fresh frozen plasma was given for TPE at a volume of 40 mL per kg of body weight (BW), as well as a heparin infusion for an anticoagulation at a rate of 10 U/kg/hour. The 3200 and 2900 mL mean plasma volumes were exchanged/substituted during the extracorporeal procedures.
Pharmacological treatment options for severe hypertriglyceridemia and familial chylomicronemia syndrome
Published in Expert Review of Clinical Pharmacology, 2018
Rabia Chaudhry, Adie Viljoen, Anthony S. Wierzbicki
Severe hypertriglyceridemia is associated with the only reason for emergency admission in lipidology [3,12,18]. There is an ‘exponential’ risk of increasing TG concentrations with risk of pancreatitis but a specific treatment threshold is difficult to set [25]. Hypertriglyceridemia is associated with a risk of pancreatitis that increases markedly with plasma TG concentrations above 20 mmol/L (~1800 mg/dL) though most cases occur with TG > 35 mmol/L (3000 mg/dL) [26]. Given large biological variance in TG levels many guidelines suggest 20 mmol/L or 2000 mg/dL as an absolute treatment threshold [3,6,27]. Treatment targets are more controversial as there is little systematic evidence base for the treatment of FCS. Any available evidence base is related to CVD risk and not to pancreatitis. Many clinicians would consider TG concentrations of <10 mmol/L (~900 mg/dL) as desirable and levels <5 mmol/L (~400 mg/dL) ideal [18]. However, regulatory bodies and commercial studies aim for TG goals set from studies in CVD or the metabolic syndrome and typically report achievement of TGs <2.3 mmol/L (200 mg/dL) or <1.7 mmol/L (150 mg/dL) [28]. Most patients with FCS are at low risk for atherosclerosis unless they develop diabetes but those with apoA5 mutations may be a higher risk of developing CVD as the presence of mutations in apoA5 correlates with a higher risk of CVD in genetic epidemiological studies [24]. There is no target for TGs in any recent CVD guideline but risk of CVD is included within recommendations for reduction of non-HDL cholesterol to <2.5–3.0 mmol/L (100–120 mg/dL).
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