Abstract
Objective
To examine the association of 2 common polymorphisms in high-density lipoprotein (HDL)-related
genes, namely, cholesterol ester transfer protein CETP Taq1B (rs708272) and endothelial
lipase LIPG Thr111Ile (rs2000813), with glycated hemoglobin (A1C), blood lipid levels
and the risk for type 2 diabetes in a group of hyperlipidemic patients from northern
Greece.
Methods
We categorized 175 patients with hyperlipidemia into 2 subgroups according to the
presence or absence of type 2 diabetes, defined as a recent diagnosis, A1C >6.5% and/or
fasting glucose >126 mg/dL. Genotypes for the 2 polymorphisms studied were determined
by polymerase chain reaction-restriction fragment length polymorphism. Both polymorphisms
were analyzed by multivariate and univariate analyses of baseline A1C levels and plasma
lipids. The genotype and allele frequencies of the 2 subgroups were compared.
Results
The CETP Taq1B polymorphism was associated with HDL-cholesterol (HDL-C) and A1C levels,
but this association was affected by type 2 diabetes; the association with A1C levels
was significant only in type 2 diabetes (p=0.005), whereas the association with HDL-C
occurred only in the subgroup without type 2 diabetes (p<0.001). LIPG Thr111Ile did
not affect plasma HDL-C or A1C levels independently but appeared to modulate their
association with CETP Taq1B, and LIPG 111IleIle homozygotes tended to be present at
a higher frequency in the hyperlipidemic patients with type 2 diabetes compared to
the hyperlipidemic patients without type 2 diabetes (p=0.056).
Conclusions
In hyperlipidemic patients, apart from its known association with HDL-C, CETP Taq1B
is also associated with A1C levels, and both associations are modified by type 2 diabetes
and LIPG Thr111Ile.
Résumé
Objectif
Examiner l'association entre 2 polymorphismes communs dans les gènes liés au cholestérol
à lipoprotéines de haute densité (HDL), à savoir, le Taq1B de la protéine de transfert
des esters de cholestérol, CETP (rs708272) et le Thr111Ile de la lipase endothéliale,
LIPG (rs2000813), et les concentrations sanguines de l'hémoglobine glyquée (A1c) et
des lipides, et le risque de diabète de type 2 chez un groupe de patients hyperlipidémiques
du nord de la Grèce.
Méthodes
Nous avons réparti 175 patients atteints d'hyperlipidémie en 2 sous-groupes selon
la présence ou l'absence de diabète de type 2, défini par un diagnostic récent, d'une
A1c>6,5 % et/ou d'une glycémie à jeun>126 mg/dl. Nous avons déterminé les génotypes
des 2 polymorphismes étudiés par la technique de réaction en chaîne de la polymérase–polymorphisme
de longueur des fragments de restriction. Nous avons analysé les 2 polymorphismes
au moyen d'analyses multivariées et univariées des concentrations initiales d'A1c
et des lipides plasmatiques. Nous avons comparé les fréquences des génotypes et des
allèles des 2 sous-groupes.
Résultats
Le polymorphisme Taq1B de la CETP était associé aux concentrations de cholestérol
HDL (HDL-C) et d'A1c, mais cette association était affectée par le diabète de type
2; l'association avec les concentrations d'A1c était seulement significative lors
de diabète de type 2 (p=0,005), alors que l'association avec le HDL-C apparaissait
seulement chez le sous-groupe atteint du diabète de type 2 (p<0,001). Le Thr111Ile
de la LIPG n'affectait pas les concentrations plasmatiques du HDL-C ou de l'A1c de
façon indépendante, mais semblait moduler leur association avec le Taq1B de la CEPT,
et les homozygotes 111IleIle de la LIPG avaient tendance à être présents selon une
fréquence plus élevée chez les patients hyperlipidémiques atteints du diabète de type
2 comparativement aux patients hyperlipidémiques non atteints du diabète de type 2
(p=0,056).
Conclusions
Chez les patients hyperlipidémiques, le Taq1B de la CETP, excepté son association
connue avec le HDL-C, est également associé aux concentrations d'A1c, mais les deux
associations sont modifiées par le diabète de type 2 et le Thr111Ile de la LIPG.
Keywords
Mots clés
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References
- New insights into the pathophysiology of dyslipidemia in type 2 diabetes.Atherosclerosis. 2015; 239: 483-495
- The Taq1B-variant in the cholesteryl ester transfer protein gene and the risk of metabolic syndrome.Obesity. 2008; 16: 912-922
- Interaction between cholesteryl ester transfer protein and hepatic lipase encoding genes and the risk of type 2 diabetes: Results from the Telde study.PLoS ONE. 2011; 6: e27208
- Epistatic effect of cholesteryl ester transfer protein and hepatic lipase on serum high-density lipoprotein cholesterol levels.J Clin Endocrinol Metab. 2007; 92: 2680-2687
- High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants.Atherosclerosis. 2008; 200: 161-167
- Cholesteryl ester transfer protein and hepatic lipase gene polymorphisms: Effects on hepatic mRNA levels, plasma lipids and carotid atherosclerosis.Atherosclerosis. 2011; 216: 374-380
- Update on the role of endothelial lipase in high-density lipoprotein metabolism, reverse cholesterol transport, and atherosclerosis.Circ J. 2010; 74: 2263-2270
- Genetic and structure-function studies of missense mutations in human endothelial lipase.PLoS ONE. 2013; 8: e55716
- Association of endothelial lipase Thr111Ile polymorphism with lipid metabolism and microvascular complications in type 2 diabetic patients.Diabetes Metab. 2011; 37: 64-71
- Association of endothelial lipase Thr111Ile polymorphism with proliferative retinopathy in type 2 diabetes patients.Diabetes Metab. 2014; 40: 452-458
- Role of hepatic lipase and endothelial lipase in high-density lipoprotein-mediated reverse cholesterol transport.Curr Atheroscler Rep. 2011; 13: 257-265
- Endothelial lipase and reverse cholesterol transport in type 2 diabetes mellitus.J Diabetes Investig. 2010; 1: 111-116
- The frequency of the cholesteryl ester transfer protein-TaqI B2 allele is lower in African Americans than in Caucasians.Atherosclerosis. 2002; 163: 169-174
- Identification of genetic variants in endothelial lipase in persons with elevated high-density lipoprotein cholesterol.Circulation. 2002; 106: 1321-1326
- Genetic-epidemiological evidence on genes associated with HDL cholesterol levels: A systematic in-depth review.Exp Gerontol. 2009; 44: 136-160
- Common variation in the CETP gene and the implications for cardiovascular disease and its treatment: An updated analysis.Pharmacogenomics. 2008; 9: 747-763
- Cholesteryl ester transfer protein TaqI B and lipoprotein lipase Ser447Ter gene polymorphisms are not associated with ischaemic stroke in Greek patients.Neurosci Lett. 2005; 384: 102-105
- Mining the LIPG allelic spectrum reveals the contribution of rare and common regulatory variants to HDL cholesterol.PLoS Genet. 2011; 7: e1002393
- Contribution of the cholesteryl ester transfer protein gene TaqIB polymorphism to the reduced plasma HDL-cholesterol levels found in abdominal obese men with the features of the insulin resistance syndrome.Int J Obes Relat Metab Disord. 1999; 23: 918-925
- Influence of menopause and cholesteryl ester transfer protein (CETP) TaqIB polymorphism on lipid profile and HDL subpopulations distribution in women with and without type 2 diabetes.Atherosclerosis. 2010; 210: 294-301
- Association between HDL-cholesterol and the Taq1B polymorphism in the cholesterol ester transfer protein gene in obese women.Atherosclerosis. 2002; 162: 419-424
- HDL and glucose metabolism: Current evidence and therapeutic potential.Front Pharmacol. 2015; 6: 258
- Interaction between dietary fat intake and the cholesterol ester transfer protein TaqIB polymorphism in relation to HDL-cholesterol concentrations among US diabetic men.Am J Clin Nutr. 2007; 86: 1524-1529
- The CETP TaqIB polymorphism is associated with the risk of sudden death in type 2 diabetic patients.Diabetes Care. 2007; 30: 2863-2867
- Pleiotropic effects of lipid genes on plasma glucose, HbA1c, and HOMA-IR levels.Diabetes. 2014; 63: 3149-3158
- The associations between endothelial lipase 584C/T polymorphism and HDL-C level and coronary heart disease susceptibility: A meta-analysis.Lipids Health Dis. 2014; 13: 85
- Role of SN1 lipases on plasma lipids in metabolic syndrome and obesity.Arterioscler Thromb Vasc Biol. 2014; 34: 669-675
- Endothelial lipase: A modulator of lipoprotein metabolism upregulated by inflammation.Trends Cardiovasc Med. 2004; 14: 202-206
- Heparanase levels are elevated in the urine and plasma of type 2 diabetes patients and associate with blood glucose levels.PLoS ONE. 2011; 6: e17312
- The function of heparanase in diabetes and its complications.Can J Diabetes. 2013; 37: 332-338
- Interleukin 6 stimulates endothelial binding and transport of high-density lipoprotein through induction of endothelial lipase.Arterioscler Thromb Vasc Biol. 2013; 33: 2699-2706
- HDL biogenesis and functions: Role of HDL quality and quantity in atherosclerosis.Atherosclerosis. 2010; 208: 3-9
Article info
Publication history
Published online: August 30, 2016
Accepted:
January 18,
2016
Received in revised form:
November 26,
2015
Received:
June 26,
2015
Identification
Copyright
© 2016 Canadian Diabetes Association.
