A Polynesian-specific SLC22A3 variant associates with low plasma lipoprotein(a) concentrations independent of apo(a) isoform size in males.

Autor:	Wang Q; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.; Maurice Wilkins Centre, New Zealand., McCormick S; Maurice Wilkins Centre, New Zealand.; Department of Biochemistry, University of Otago, Dunedin, New Zealand., Leask MP; University of Alabama, Birmingham, USA., Watson H; Paratene Ngata Research Centre, Ngati Porou Oranga, Te Puia Springs, New Zealand., O'Sullivan C; Maurice Wilkins Centre, New Zealand.; Moko Foundation, Kaitaia, New Zealand., Krebs JD; Centre for Endocrine, Diabetes and Obesity Research, Te Whatu Ora New Zealand Capital, Coast and Hutt Valley, Wellington, New Zealand.; Department of Medicine, University of Otago, Wellington, New Zealand., Hall R; Department of Medicine, University of Otago, Wellington, New Zealand., Whitfield P; Department of Medicine, University of Otago, Wellington, New Zealand., Merry TL; Maurice Wilkins Centre, New Zealand.; Department of Nutrition, University of Auckland, New Zealand., Murphy R; Maurice Wilkins Centre, New Zealand.; Auckland Diabetes Center, Te Whatu Ora Health New Zealand, Te Tokai Tumai, New Zealand.; Department of Medicine, University of Auckland, Auckland, New Zealand., Shepherd PR; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.; Maurice Wilkins Centre, New Zealand.
Jazyk:	angličtina
Zdroj:	Bioscience reports [Biosci Rep] 2024 Jul 31; Vol. 44 (7).
DOI:	10.1042/BSR20240403
Abstrakt:	Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle in which the apolipoprotein B component is covalently linked to apolipoprotein(a) (apo(a)). Lp(a) is a well-established independent risk factor for cardiovascular diseases. Plasma Lp(a) concentrations vary enormously between individuals and ethnic groups. Several nucleotide polymorphisms in the SLC22A3 gene associate with Lp(a) concentration in people of different ethnicities. We investigated the association of a Polynesian-specific (Māori and Pacific peoples) SLC22A3 gene coding variant p.Thr44Met) with the plasma concentration of Lp(a) in a cohort of 302 healthy Polynesian males. An apo(a)-size independent assay assessed plasma Lp(a) concentrations; all other lipid and apolipoprotein concentrations were measured using standard laboratory techniques. Quantitative real-time polymerase chain reaction was used to determine apo(a) isoforms. The range of metabolic (HbA1c, blood pressure, and blood lipids) and blood lipid variables were similar between the non-carriers and carriers in age, ethnicity and BMI adjusted models. However, rs8187715 SLC22A3 variant was significantly associated with lower Lp(a) concentrations. Median Lp(a) concentration was 10.60 nmol/L (IQR: 5.40-41.00) in non-carrier group, and was 7.60 nmol/L (IQR: 5.50-12.10) in variant carrier group (P<0.05). Lp(a) concentration inversely correlated with apo(a) isoform size. After correction for apo(a) isoform size, metabolic parameters and ethnicity, the association between the SLC22A3 variant and plasma Lp(a) concentration remained. The present study is the first to identify the association of this gene variant and low plasma Lp(a) concentrations. This provides evidence for better guidance on ethnic specific cut-offs when defining 'elevated' and 'normal' plasma Lp(a) concentrations in clinical applications. (© 2024 The Author(s).)
Databáze:	MEDLINE
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