Abstract
Aim: Our goal was to assess the population prevalence, genetics and clinical phenotypes of subjects with marked HDL deficiency. Methods: 200 subjects (26% female, mean age 52 years) with serum HDL-C < 20 mg/dL, fasting triglycerides (TG) < 600 mg/dL, C reactive protein (CRP) < 10 mg/L, myeloperoxidase (MPO) < 1000 pmoles/L, HbA1c < 8.0%, liver transaminases < 120 U/L, and not taking anabolic steroids were studied. Lipids, inflammation markers, liver enzymes, and HDL particles were assessed; and sequencing of 31 lipid metabolism genes including ABCA1, APOA1, LCAT , and LPL was done. Results: HDL-C < 20 mg/dl was observed in 473 (0.35%) men (n=135,912) and 140 (0.089%) women (n=160,964) in our population over one year. In this low HDL group, 6.4% had elevated CRP, 4.4% had abnormal liver function, 4.2% had elevated HbA1c, 1.0% had elevated MPO, 0.5% had elevated TG, and 11.5% of men were taking anabolic steroids. These subjects were excluded. The 200 subjects studied had plasma values of LDL-C 102, HDL-C 15, TG 239, and apoA-I 76 mg/dL, with a marked deficiency of very large and large α-1 and α-2 HDL. ABCA1 mutations were found in 38 subjects (19.0%; 29 heterozygotes, 6 compound heterozygotes, 3 homozygotes). APOA1 mutations were found in 10 subjects (5.0%; 9 heterozygotes, 1 homozygote). LCAT mutations were found in 17 subjects (8.5%; 13 heterozygotes, 3 compound heterozygotes, 1 homozygote). In addition, 11 subjects (5.5%) had the LPL N318S variant, and 13 subjects (6.5%) had the ABCA1 c.-279 C>G variant. Premature coronary heart disease (CHD) was observed in some subjects with ABCA1 and APOA1 mutations. Neuropathy was observed in some subjects with ABCA1 mutations, and kidney failure was observed in the subject with the homozygous LCAT mutation. Conclusions: Marked HDL deficiency occurred in 0.2% of our population and can be associated with liver disease, inflammation, diabetes, severe hypertriglyceridemia, and the use of anabolic steroids. In the absence of these conditions, mutations in ABCA1, APOA1, or LCAT were found in 32% of subjects studied. Premature CHD was seen in some subjects with ABCA1 or APOA1 mutations, neuropathy was seen in some subjects with ABCA1 mutations, and kidney failure was observed in some subjects with LCAT mutations.
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