Evaluation of apolipoprotein A5 variants: A cohort of patients with severe hypertriglyceridemia from Turkiye.

BACKGROUND: This study aims to show the clinical and biochemical features in patients with severe hypertriglyceridemia (HTG) associated with rare variants in the apolipoprotein A-V (APOA5) gene. MATERIALS AND METHODS: Demographics, blood lipid levels, body mass index (BMI) and APOA5 mutation subtypes were collected from the endocrinology clinic registry and analyzed for a retrospective cohort study of ten patients with severe HTG and APOA5 gene variants. RESULTS: Of the 10 cases, four were female, and six were male. The median age was 45.0 years (min-max: 21-60 years), the median triglyceride was 2429.5 mg/dL (27.5 mmol/L) (min-max: 1351-4087 mg/dL, 15.3-46.2 mmol/L), and the mean BMI was calculated as 30.4 ± 4.4 kg/m2 (min-max: 24.9-41.0 kg/m2). Four cases had diabetes mellitus (DM); two were on intensive insulin therapy, and two were on basal insulin therapy. The mean hemoglobin A1c was 9.2 ± 1.2 % (min-max: 8.3-11.0 %). Among the study group, eight different APOA5 gene mutations were detected. These variants were heterozygous in 2 patients and homozygous (bi-allelic) in 8 patients. One patient was homozygous for APOA5 p.Ser19Trp, a relatively common polymorphism that is a risk variant for HTG. CONCLUSION: We report a cohort of patients with biallelic and single copy APOA5 variants, who were diagnosed later in life. Most had secondary factors, such as DM or obesity with increased BMI. Most rare APOA5 variants found in our patients were of uncertain significance. Our results add to the growing evidence that rare variants in certain candidate genes may predispose to developing HTG, together with secondary factors such as obesity. The genetic basis of HTG in many other patients is still unknown and remains the subject of further investigation.

Acromegaly is associated with high fibroblast growth factor-21 levels.

PURPOSE: Fibroblast growth factor-21 (FGF-21) is a member of fibroblast growth factor family. Both growth hormone (GH) and FGF-21 take place in the regulation of glucose and lipid metabolism. We aimed to investigate FGF-21 levels in acromegaly which is characterized by excess GH levels and is associated with comorbidities and altered body composition. METHODS: We studied 43 subjects (21 females and 22 males, mean age of 50.0 ± 12.8) with acromegaly. The control group consisted of 40 gender- and age-matched subjects (25 females and 15 males, mean age of 48.8 ± 8.8). Acromegaly patients were classified into two groups; active acromegaly (AA; n = 26) and controlled acromegaly (CA; n = 17). Metabolic, anthropometric and laboratory values of subjects were recorded. FGF-21 level was measured by ELISA assay. RESULTS: Median FGF-21 levels were significantly higher in acromegaly group compared to control group (85.5 vs. 59.0 pg/mL, p = 0.02, respectively). In the multiple regression model, FPG, A1c, HOMA-IR, glucose intolerance, BMI, visceral fat, hs-CRP, presence of hypertension, dyslipidemia and acromegaly were included as independent variables to explain variability of plasma FGF-21 levels in whole study group. The presence of acromegaly was the only determinant of increased FGF-21 levels in the whole study group (ß coefficient = 0.253, p = 0.006). CONCLUSION: FGF-21 levels were increased significantly in acromegaly group. Increased FGF-21 levels were significantly and independently associated with the state of acromegaly. Acromegaly may also be a FGF-21 resistance state independent from insulin resistance, glucose intolerance, obesity, hypertension and dyslipidemia.