R1615P: A novel mutation in ABCA1 associated with low levels of HDL and type II diabetes mellitus

Saleheen, Danish; Nazir, Aisha; Khanum, Shaheen; Haider, Shajjia Razi; Frossard, Philippe

doi:10.1016/j.ijcard.2005.06.059

Cited by 17 publications

(13 citation statements)

References 5 publications

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“…At least 2 pathogenic ABCA1 mutations have been reported to be associated with T2D in particular patients. One 33-year-old male with T2D and very low HDL cholesterol (0.26 mmol/l) was found to be heterozygous for a novel R1615P missense mutation in ABCA1 (59). An additional patient with T2D was found to have a mutation in exon 4 of the ABCA1 gene (60).…”

Section: Figurementioning

confidence: 99%

Cholesterol in islet dysfunction and type 2 diabetes

Brunham¹,

Kruit²,

Verchere³

et al. 2008

J. Clin. Invest.

136

104

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Section: Figurementioning

confidence: 99%

Cholesterol in islet dysfunction and type 2 diabetes

Brunham¹,

Kruit²,

Verchere³

et al. 2008

J. Clin. Invest.

136

104

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“…Interestingly, the ABCA1 receptor is considered a major factor in the maintenance of the plasma HDL-C concentration and for cell cholesterol efflux essential to prevent pancreatic islet lipid accumulation [5] and carriers of loss-of-function mutations in ABCA1 show impaired insulin secretion with [6] or without insulin resistance [7]. Also, certain ABCA1 genotypes have been related to increased risk of diabetes mellitus in humans with [8,9] or without [10] low HDL concentrations in plasma. Mice lacking Abca1 have impaired glucose tolerance [11] although in the LDLr knockout mouse model no associations were observed between the quantitative trait loci of atherosclerosis and levels of total cholesterol, HDL-C, insulin or body weight [12].…”

Section: Introductionmentioning

confidence: 99%

Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects

Leança

Nunes

Panzoldo

et al. 2013

Cardiovasc Diabetol

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BackgroundWe have searched if plasma high density lipoprotein-cholesterol (HDL-C) concentration interferes simultaneously with whole-body cholesterol metabolism and insulin sensitivity in normal weight healthy adult subjects.MethodsWe have measured the activities of several plasma components that are critically influenced by insulin and that control lipoprotein metabolism in subjects with low and high HDL-C concentrations. These parameters included cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), lecithin cholesterol acyl transferase (LCAT), post-heparin lipoprotein lipase (LPL), hepatic lipase (HL), pre-beta-1HDL, and plasma sterol markers of cholesterol synthesis and intestinal absorption.ResultsIn the high-HDL-C group, we found lower plasma concentrations of triglycerides, alanine aminotransferase, insulin, HOMA-IR index, activities of LCAT and HL compared with the low HDL-C group; additionally, we found higher activity of LPL and pre-beta-1HDL concentration in the high-HDL-C group. There were no differences in the plasma CETP and PLTP activities.ConclusionsThese findings indicate that in healthy hyperalphalipoproteinemia subjects, several parameters that control the metabolism of plasma cholesterol and lipoproteins are related to a higher degree of insulin sensitivity.

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“…Part of the increased cardiovascular risk associated with diabetes is due to genetic variations that influence both glucose homeostasis and the development of atherosclerosis. A few rare gene mutations result in both early coronary heart disease and T2DM that are observable as Mendelian traits segregatingin families, which include LRP6 2 , ABCA1 3,4 , and APOB 5 . Recent genome-wide association studies (GWAS) have identified dozens of common genetic variants for both atherosclerosis and T2DM (http://www.genome.gov/GWAStudies/).…”

Section: Introductionmentioning

confidence: 99%

Genetic Analysis of Atherosclerosis and Glucose Homeostasis in an Intercross Between C57BL/6 and BALB/cJ Apolipoprotein E–Deficient Mice

Zhang

Rowlan

Wang

et al. 2012

Circ Cardiovasc Genet

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Background Diabetic patients have an increased risk of developing atherosclerosis and related complications compared to non-diabetic individuals. The increased cardiovascular risk associated with diabetes is due in part to genetic variations that influence both glucose homeostasis and atherosclerotic lesion growth. Mouse strains C57BL/6J (B6) and BALB/cJ (BALB) exhibit distinct differences in fasting plasma glucose and atherosclerotic lesion size when deficient in apolipoprotein E (Apoe−/− . Quantitative trait locus (QTL) analysis was performed to determine genetic factors influencing the two phenotypes. Methods and Results 266 female F2 mice were generated from an intercross between B6.Apoe−/− and BALB.Apoe−/− mice and fed a Western diet for 12 weeks. Atherosclerotic lesions in the aortic root, fasting plasma glucose, and body weight were measured. 130 microsatellite markers across the entire genome were genotyped. Four significant QTLs, Ath1 on chromosome (Chr) 1, Ath41 on Chr2, Ath42 on Chr5, and Ath29 on Chr9, and one suggestive QTL on Chr4, were identified for atherosclerotic lesion size. Four significant QTLs, Bglu3 and Bglu12 on Chr1, Bglu13 on Chr5, Bglu15 on Chr12, and two suggestive QTLs on Chr9 and Chr15 were identified for fasting glucose levels on the chow diet. Two significant QTLs, Bglu3 and Bglu13, and one suggestive locus on Chr8 were identified for fasting glucose on the Western diet. One significant locus on Chr1 and two suggestive loci on Chr9 and Chr19 were identified for body weight. Ath1 and Ath42 coincided with Bglu3 and Bglu13, respectively, in the confidence interval. Conclusions We have identified novel QTLs that have major influences on atherosclerotic lesion size and glucose homeostasis. The colocalization of QTLs for atherosclerosis and diabetes suggests possible genetic connections between the two diseases.

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R1615P: A novel mutation in ABCA1 associated with low levels of HDL and type II diabetes mellitus

Cited by 17 publications

References 5 publications

Cholesterol in islet dysfunction and type 2 diabetes

Cholesterol in islet dysfunction and type 2 diabetes

Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects

Genetic Analysis of Atherosclerosis and Glucose Homeostasis in an Intercross Between C57BL/6 and BALB/cJ Apolipoprotein E–Deficient Mice

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