Novel polymorphisms associated with hyperalphalipoproteinemia and apparent cardioprotection

Hyperalphalipoproteinemia (HALP) is inversely correlated with coronary heart disease (CHD) although genetic variants associated with high serum levels of high-density lipoprotein cholesterol (HDL-C) have not been shown to be cardioprotective. The objective of the study was to uncover novel genetic v...

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Bibliographic Details
Published in:Journal of clinical lipidology 2018-01, Vol.12 (1), p.110-115
Main Authors: Oates, Connor P., Koenig, Darya, Rhyne, Jeffrey, Bogush, Nikolay, O'Connell, Jeffrey, Mitchell, Braxton D., Miller, Michael
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
CAD
cardioprotection
Cholesterol, HDL - blood
Exome Sequencing
Female
Gene Frequency
Glucuronosyltransferase - genetics
HALP
HDL-C
Humans
Hyperalpha
Hyperlipoproteinemias - epidemiology
Hyperlipoproteinemias - genetics
Hyperlipoproteinemias - pathology
Male
Middle Aged
Myelin and Lymphocyte-Associated Proteolipid Proteins - genetics
Pedigree
Phenotype
Polymorphism, Single Nucleotide
Receptors, Steroid - genetics
Triglycerides - blood
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Summary:Hyperalphalipoproteinemia (HALP) is inversely correlated with coronary heart disease (CHD) although genetic variants associated with high serum levels of high-density lipoprotein cholesterol (HDL-C) have not been shown to be cardioprotective. The objective of the study was to uncover novel genetic variants associated with HALP and possibly with reduced risk of CHD. Exome sequencing data, HDL-C, and triglyceride levels were analyzed in 1645 subjects. They included the University of Maryland outpatients with high HDL-C (n = 12), Cardiovascular Health Study (n = 210), Jackson Heart Study (n = 402), Multi-Ethnic Study of Atherosclerosis (n = 404), Framingham Heart Study (n = 463), and Old Order Amish (n = 154). Novel nonsynonymous single-nucleotide polymorphisms (nsSNPs) were identified in men and women with primary HALP (mean HDL-C, 145 ± 30 mg/dL). Using PolyPhen-2 and Combined Annotation Dependent Depletion to estimate the predictive effect of each nsSNP on the gene product, rare, deleterious polymorphisms in UGT1A3, PLLP, PLEKHH1, ANK2, DIS3L, ACACB, and LRP4 were identified in 16 subjects with HALP but not in any tested subject with low HDL-C (
ISSN:1933-2874
1876-4789
DOI:10.1016/j.jacl.2017.10.021