Variant rs10911021 that associates with coronary heart disease in type 2 diabetes, is associated with lower concentrations of circulating HDL cholesterol and large HDL particles but not with amino acids

Beaney, Katherine E.; McLachlan, Stela; Wannamethee, SG; Jefferis, Barbara J.; Whincup, Peter H.; Ben-Shlomo, Yoav; Price, Jackie F.; Wong, Andrew; Ong, Ken K.; Hardy, Rebecca; Kuh, Diana; Kivimäki, Mika; Kangas, Antti J.; Soininen, Pasi; Ala‐Korpela, Mika; Drenos, Fotios; Humphries, Steve E.

doi:10.1186/s12933-016-0435-0

Cited by 14 publications

(10 citation statements)

References 30 publications

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“…Our results showed that 2 SNPs (rs2285666 and rs4646142) was not associated with T2D (see Additional file 1 : Table S4) but exhibited association with T2D with moderate risk of atherogenic dyslipidemia (see Additional file 1 : Table S6, S7), which were consistent with previously reported association of the loci with ASCVD (e.g., coronary heart disease [ 32 ], ischemic stroke [ 33 ]) in T2D patients as well as cardiovascular death in European females [ 34 ]. Similar effects also existed in between rs10911021 and CAD in T2D [ 35 ] as well as between CLOCK polymorphism and stroke in T2D patients [ 36 ]. According to the 2014 NLA recommendations [ 37 ], carotid arteriosclerosis stenosis (CAS) ≥ 50% is defined as a new type of ASCVD.…”

Section: Discussionmentioning

confidence: 67%

ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus

Cheng

Guan

et al. 2018

Cardiovasc Diabetol

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BackgroundType 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D.Methods275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry.ResultsACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P < 0.05). The 8 diabetic risk related ACE2 SNPs were further associated with diabetic related cardiovascular complications or events but exhibited heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs (all P < 0.05) were associated with increased SBP except rs1978124 and rs2074192, while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P < 0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at least correlated with one type of dyslipidemia (all P < 0.05). In particular, rs879922 were simultaneously correlated with four type of dyslipidemia (all P < 0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid arteriosclerosis stenosis (CAS) ≥ 50% (both P < 0.05). Fourthly, ACE2 SNP rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU (all P < 0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188 and rs879922 were linked to heavier LVMI (all P < 0.05), but only rs4240157, rs4646156 and rs4646188 were associated with lower LVEF (all P < 0.05).ConclusionACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0771-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 67%

ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus

Cheng

Guan

et al. 2018

Cardiovasc Diabetol

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“…Genome-wide association studies have provided good insight into the relationship between lipid metabolism and CAD [ 22 , 23 ]. From these studies the cardiovascular phenotype of genetic variants seems to depend on ethnicity or the presence of diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus

Ahn

Kim

et al. 2017

Cardiovasc Diabetol

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ContextA previous genome-wide association study showed that a genetic variant of sortilin was associated with the risk of coronary artery disease (CAD). However, the role of circulating sortilin is still unknown. We investigated the potential role of plasma sortilin as a biomarker for CAD and diabetes mellitus.MethodsWe enrolled statin-naïve subjects with CAD (n = 31) who underwent coronary artery bypass surgery and control subjects (n = 116) who were free from CAD as evaluated by coronary CT angiography. The presence of diabetes mellitus was evaluated and plasma sortilin levels were measured with a commercial ELISA kit.ResultsPlasma sortilin levels were higher in subjects with CAD and subjects with diabetes mellitus than in those without CAD or diabetes mellitus. Subjects in the highest sortilin tertile group were older and had higher glucose and HbA1c levels, but lipid profiles in the three tertile groups were comparable. Multivariable logistic regression analysis revealed that sortilin levels were independently associated with CAD. In addition, the receiver operating characteristic curve analysis showed that plasma sortilin levels could identify the presence of CAD or diabetes mellitus.ConclusionsElevated circulating sortilin levels are associated with CAD and diabetes mellitus and can be used as a biomarker of both diseases in statin-naïve subjects.

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“…Further studies confirmed the association of the rs10911021 GLUL variant with type 2 DM, and demonstrated that this polymorphism does not affect amino acid metabolism. However, although apparently counterintuitive, it is associated with lower HDL cholesterol levels, and large HDL particles ( 45 ).…”

Section: Genetic Aspectsmentioning

confidence: 99%

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

et al. 2018

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Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.

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Variant rs10911021 that associates with coronary heart disease in type 2 diabetes, is associated with lower concentrations of circulating HDL cholesterol and large HDL particles but not with amino acids

Cited by 14 publications

References 30 publications

ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus

ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus

Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

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