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Novel polymorphisms associated with hyperalphalipoproteinemia and apparent cardioprotection.
Tuesday,2018-01-16 18:27 America/Los_Angeles — ecterry
| Title | Novel polymorphisms associated with hyperalphalipoproteinemia and apparent cardioprotection. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Oates, CP, Koenig, D, Rhyne, J, Bogush, N, O'Connell, J, Mitchell, BD, Miller, M |
| Journal | J Clin Lipidol |
| Date Published | 2017 Nov 21 |
| ISSN | 1933-2874 |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>OBJECTIVE: </b>The objective of the study was to uncover novel genetic variants associated with HALP and possibly with reduced risk of CHD.</p><p><b>METHODS: </b>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).</p><p><b>RESULTS: </b>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 (<40 mg/dL). In addition, a single novel polymorphism, rs376849274, was found in OSBPL1A. The majority of these candidate genes have been implicated in fat and lipid metabolism, and none of these subjects has a history of CHD despite 75% of subjects having risk factors for CHD. Overall, the probability of finding these nsSNPs in a non-high HDL-C population ranges from 1 × 10-17 to 1 × 10-25.</p><p><b>CONCLUSION: </b>Novel functional polymorphisms in 8 candidate genes are associated with HALP in the absence of CHD. Future study is required to examine the extent to which these genes may affect HDL function and serve as potential therapeutic targets for CHD risk reduction.</p> |
| DOI | 10.1016/j.jacl.2017.10.021 |
| Alternate Journal | J Clin Lipidol |
| PubMed ID | 29198934 |
| Grant List | R01 HL061369 / HL / NHLBI NIH HHS / United States R21 HL094980 / HL / NHLBI NIH HHS / United States |
ePub date:
17/11