Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/83420
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Type: Journal article
Title: Association of PARL rs3732581 genetic variant with insulin levels, metabolic syndrome and coronary artery disease
Author: Powell, B.
Wiltshire, S.
Arscott, G.
McCaskie, P.
Hung, J.
McQuillan, B.
Thompson, P.
Carter, K.
Palmer, L.
Beilby, J.
Citation: Human Genetics, 2008; 124(3):263-270
Publisher: Springer
Issue Date: 2008
ISSN: 0340-6717
1432-1203
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Responsibility: 
Brenda L. Powell, Steven Wiltshire, Gillian Arscott, Pamela A. McCaskie, Joseph Hung, Brendan M. McQuillan, Peter L. Thompson, Kim W. Carter, Lyle J. Palmer, John P. Beilby
Abstract: PARL (presenilin-associated rhomboid-like) is a mitochondrial protein involved in mitochondrial membrane remodelling, and maps to a quantitative trait locus (3q27) associated with metabolic traits. Recently the rs3732581 (Leu262Val) variant was found to be associated with increased levels of plasma insulin, a finding not replicated in a larger cohort. The aim of the current study was to investigate the associations between rs3732581 and levels of plasma insulin, metabolic syndrome (MetS) and its components, and cardiovascular disease. The CUPID population consisted of 556 subjects with angiographically proven CAD and the CUDAS cohort consisted of 1,109 randomly selected individuals from Perth, Western Australia. Samples were genotyped using mutation-specific PCR. No significant associations were observed between rs3732581 and levels of plasma insulin, glucose, BMI or MetS in either population. However, carriers of the minor allele had significantly lower mean intima-media thickness (IMT) [0.69 mm, 95% CI (0.69, 0.70 mm); P = 0.004], compared with major allele homozygotes [mean IMT = 0.71 mm, 95% CI (0.70, 0.72 mm)] in the CUDAS population. Further analysis using a recessive model showed homozygous carriers of the minor allele were predisposed to CAD [OR 1.55, 95% CI (1.11, 2.16); P = 0.01]. Despite the functional evidence for a role of PARL in regulating insulin levels, no association with rs3732581 was found in the current study. Additionally, there were no associations with glucose levels, BMI or MetS. There were significant effects of the variant on mean IMT and risk of CAD. A role for PARL in metabolic conditions cannot be excluded and more comprehensive genetic studies are warranted.
Keywords: Humans; Metabolic Syndrome X; Insulin; Metalloproteases; Mitochondrial Proteins; Body Mass Index; Risk; Cohort Studies; Mutation; Adult; Aged; Middle Aged; Female; Male; Coronary Artery Disease; Genetic Variation
Rights: © Springer-Verlag 2008
RMID: 0020136659
DOI: 10.1007/s00439-008-0552-2
Appears in Collections:Medicine publications

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