A rare splice donor mutation in the haptoglobin gene associates with blood lipid levels and coronary artery disease.
Hum Mol Genet
; 26(12): 2364-2376, 2017 06 15.
Article
em En
| MEDLINE
| ID: mdl-28398513
ABSTRACT
Common sequence variants at the haptoglobin gene (HP) have been associated with blood lipid levels. Through whole-genome sequencing of 8,453 Icelanders, we discovered a splice donor founder mutation in HP (NM_001126102.1c.190 + 1G > C, minor allele frequency = 0.56%). This mutation occurs on the HP1 allele of the common copy number variant in HP and leads to a loss of function of HP1. It associates with lower levels of haptoglobin (P = 2.1 × 10-54), higher levels of non-high density lipoprotein cholesterol (ß = 0.26 mmol/l, P = 2.6 × 10-9) and greater risk of coronary artery disease (odds ratio = 1.30, 95% confidence interval 1.10-1.54, P = 0.0024). Through haplotype analysis and with RNA sequencing, we provide evidence of a causal relationship between one of the two haptoglobin isoforms, namely Hp1, and lower levels of non-HDL cholesterol. Furthermore, we show that the HP1 allele associates with various other quantitative biological traits.
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1
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
/
Haptoglobinas
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article