Evaluation of pleiotropic effects among common genetic loci identified for cardio-metabolic traits in a Korean population

Kim, Yun Kyoung; Hwang, Mi Yeong; Kim, Young Jin; Moon, Sanghoon; Han, Sohee; Kim, Bong-Jo

doi:10.1186/s12933-016-0337-1

Cited by 20 publications

(19 citation statements)

References 38 publications

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“…However, the association of ACE2 SNPs with T2D and T2D related cardiovascular complications (e.g., hypertension and dyslipidemia) or events (e.g., ASCVD) in Chinese population are rarely reported. Theoretically, there may be common genetic basis between them [ 8 , 12 , 13 ] manifesting the characteristics of ethnic-specific genetic pleiotropy among cardio-metabolic traits [ 14 ]. In this study we investigated possible associations between ACE2 gene variation and cardiovascular risk in Uygur patients with type 2 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

Cheng

Guan

et al. 2018

Cardiovasc Diabetol

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“…In Table 1 , studies investigating common and rare variants in association with hypertension andBP phenotypes and through exome array approaches are listed. Most publications [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]; ( Table 1 ) took advantage of the Illumina HumanExome BeadChip (Exome Chip; Illumina, Inc., San Diego, CA, USA).…”

Section: Resultsmentioning

confidence: 99%

Advances in the Genetics of Hypertension: The Effect of Rare Variants

Russo

Gaetano

Cugliari

et al. 2018

IJMS

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Worldwide, hypertension still represents a serious health burden with nine million people dying as a consequence of hypertension-related complications. Essential hypertension is a complex trait supported by multifactorial genetic inheritance together with environmental factors. The heritability of blood pressure (BP) is estimated to be 30–50%. A great effort was made to find genetic variants affecting BP levels through Genome-Wide Association Studies (GWAS). This approach relies on the “common disease–common variant” hypothesis and led to the identification of multiple genetic variants which explain, in aggregate, only 2–3% of the genetic variance of hypertension. Part of the missing genetic information could be caused by variants too rare to be detected by GWAS. The use of exome chips and Next-Generation Sequencing facilitated the discovery of causative variants. Here, we report the advances in the detection of novel rare variants, genes, and/or pathways through the most promising approaches, and the recent statistical tests that have emerged to handle rare variants. We also discuss the need to further support rare novel variants with replication studies within larger consortia and with deeper functional studies to better understand how new genes might improve patient care and the stratification of the response to antihypertensive treatments.

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“…The combined associations of LIPC SNPs with insulin surrogate markers that based on both metabolic and adiposity status are noteworthy. Shared common variants have similarly been reported between lipid genes and glucose metabolism, inflammation, BMI, cardiometabolic traits, and coronary artery disease [ 20 , 40 , 44 – 46 ]. Pickrell et al [ 21 ] developed a method of detecting pairs of traits that exhibited an asymmetry in the effect sizes of associated variants, which is more consistent with a causal relationship between the traits and the authors indicated that an elevated BMI causally increases TG levels, but the reverse is not true.…”

Section: Discussionmentioning

confidence: 99%

LIPC variants as genetic determinants of adiposity status, visceral adiposity indicators, and triglyceride-glucose (TyG) index-related parameters mediated by serum triglyceride levels

Teng

et al. 2018

Diabetol Metab Syndr

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BackgroundVisceral adiposity indicators and the product of triglyceride and fasting plasma glucose (TyG) index-related parameters are effective surrogate markers for insulin resistance (IR) and are predictors of metabolic syndrome and diabetes mellitus. However, their genetic determinants have not been previously reported. Pleiotropic associations of LIPC variants have been observed in lipid profiles and atherosclerotic cardiovascular diseases. We aimed to investigate LIPC polymorphisms as the genetic determinants of adiposity status, visceral adiposity indicators and TyG index-related parameters.MethodsA total of 592 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs).ResultsThe LIPC SNPs rs2043085 and rs1532085 were significantly associated with body mass index (BMI), waist circumference (WC), lipid accumulation product, visceral adiposity index, and TyG index-related parameters [including the TyG index, TyG with adiposity status (TyG-BMI), and TyG-WC index], whereas the rs1800588 SNP was only significantly associated with the TyG index. The associations became nonsignificant after further adjustment for serum TG levels. No significant association was observed between any the studied LIPC SNPs and IR status.ConclusionOur data revealed a pleiotropic association between the LIPC variants and visceral adiposity indicators and TyG index-related parameters, which are mediated by serum TG levels.Electronic supplementary materialThe online version of this article (10.1186/s13098-018-0383-9) contains supplementary material, which is available to authorized users.

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Evaluation of pleiotropic effects among common genetic loci identified for cardio-metabolic traits in a Korean population

Cited by 20 publications

References 38 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

Advances in the Genetics of Hypertension: The Effect of Rare Variants

LIPC variants as genetic determinants of adiposity status, visceral adiposity indicators, and triglyceride-glucose (TyG) index-related parameters mediated by serum triglyceride levels

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