HDL Deficiency and Heart Disease Associated with A Novel Apolipoprotein A-I Truncation

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 723-745-Lipids: Fatty Liver Disease & Lipodystrophies
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-735
Pimjai Anthanont*1, Esther Youngjy Lee1, Eliana Polisecki2, Bela F. Asztalos1 and Ernst John Schaefer1
1Cardiovascular Research Clinic, Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 2Boston Heart Diagnostics, Framingham, MA
Introduction: Marked high density lipoprotein (HDL) deficiency (HDL cholesterol < 10 mg/dl) is observed with severe liver disease, marked hypertriglyceridemia, or in patients with apolipoprotein (apo) A-I deficiency, apoA-I variants, Tangier disease, and lecithin:cholesterol acyl transferase (LCAT) deficiency, and may be associated with premature coronary heart disease (CHD) or kidney failure.

Clinical Case: A 68 year old man with a history of marked HDL deficiency and CHD since age 54 years (significant disease requiring quadruple coronary bypass grafting surgery). He also had a history of hypertension, but was a non-smoker, and had no history of diabetes. He had a very positive family history of CHD. Prior to being placed on lipid lowering medication his low density lipoprotein (LDL) cholesterol was 174 mg/dl, his HDL cholesterol was 13 mg/dl, and his triglycerides were 211 mg/dl. He was placed on rosuvastatin 40 mg/day, ezetimibe 10 mg/day, and fenofibrate 145 mg/day, as well as isosorbide 10 mg three times daily, metoprolol 50 mg/day, and lisinopril 20 mg/day. He had been unable to tolerate niacin therapy. He was not overweight, and a normal blood pressure. On eye examination he had significant arcus senilis.  His pulses were present throughout, but somewhat diminished. He had no evidence of hepatosplenomegaly or xanthomas. On therapy his lipid values were: total cholesterol 129 mg/dl, triglycerides 134 mg/dl, HDL-C 9 mg/dl, direct LDL-C 85 mg/dl and very low density lipoprotein-C 35 mg/dl. His apolipoprotein (apo) A-I level was 37 mg/dl (very low) his apoB level  80 mg/dl, and his lipoprotein(a) value was elevated at 60 mg/dl. His liver, kidney, and thyroid function were normal and his glycosylated hemoglobin level was 5.4%. HDL particle analysis  revealed very low levels of very small, small and medium HDL, fairly normal large HDL, but low levels of very large HDL. Analysis of his APOA1 gene revealed a novel heterozygous mutation with a C to T change at nucleotide 718, resulting in the replacement of a Q for an X at amino acid 240 in the apoA-I amino acid sequence, and the formation of a truncated apoA-I lacking the last 4 amino acids of its sequence.

Conclusion: This novel apoA-I mutation results in the formation of a truncated apoA-I that appears to have abnormal lipid binding properties, resulting in HDL deficiency, and probably impaired lipid binding and reverse cholesterol transport, as well as premature CHD.

Disclosure: EP: Employee, Boston Heart Diagnostics. BFA: Employee, Boston Heart diagnostics. EJS: Employee, Boston Heart Diagnostics. Nothing to Disclose: PA, EYL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm