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Genetic variation in CYP17A1 is associated with arterial stiffness in diabetic subjects.

ABSTRACT: Hypertension and arterial stiffness are associated with an increasing risk of diabetes and cardiovascular diseases. This study aimed to identify genetic variants affecting hypertension and arterial stiffness in diabetic subjects and to compare genetic associations with hypertension between prediabetic and diabetic subjects. A total of 1,069 participants (326 prediabetic and 743 diabetic subjects) were assessed to determine the genetic variants affecting hypertension by analyzing 52 SNPs previously reported to be associated with hypertension. Moreover, the SNPs were tested for association with hemodynamic parameters related to hypertension. Out of the 52 SNPs analyzed, four SNPs including rs5326 (DRD1), rs1004467 (CYP17A1), rs2960306 (GRK4), and rs11191548 (near NT5C2) in diabetic subjects and rs1530440 (C10orf107) in prediabetic subjects showed a modest association with hypertension (P = 0.0265, 0.0020, 0.0066, 0.0078, and 0.0015, resp; all were insignificant after Bonferroni correction). Of these SNPs, rs1004467 in CYP17A1 was significantly associated with augmentation index in diabetic subjects who were not taking antihypertensive medication (P = 0.0001; corrected P = 0.006) but not in diabetic subjects receiving antihypertensive medication. This finding suggests that certain genetic variations found in diabetic subjects may confer arterial stiffness and the development of hypertension and also be affected by antihypertensive medication.

SUBMITTER: Yang SJ

PROVIDER: S-EPMC3485973 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Genetic variation in CYP17A1 is associated with arterial stiffness in diabetic subjects.

Yang Soo Jin SJ Lee Seung-Tae ST Kim Won Jun WJ Park Se Eun SE Park Sung Woo SW Kim Jong-Won JW Park Cheol-Young CY

Experimental diabetes research 20121023

Hypertension and arterial stiffness are associated with an increasing risk of diabetes and cardiovascular diseases. This study aimed to identify genetic variants affecting hypertension and arterial stiffness in diabetic subjects and to compare genetic associations with hypertension between prediabetic and diabetic subjects. A total of 1,069 participants (326 prediabetic and 743 diabetic subjects) were assessed to determine the genetic variants affecting hypertension by analyzing 52 SNPs previous ...[more]

PMID: 23133444

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Project description:Glycated albumin (GA) exhibits atherogenic effects and increased serum GA levels are associated with the development of cardiovascular complications in diabetic patients. GA production also increases with aging, oxidative stress, and renal dysfunction. We performed this study to further ascertain the association between GA and arterial stiffness in nondiabetic chronic kidney disease (CKD) patients. We enrolled 129 nondiabetic CKD patients. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) using a volume plethysmographic instrument along with simultaneous measurements of GA. Insulin resistance was determined with the homeostatic model assessment. The estimated glomerular filtration rate was calculated using serum creatinine and cystatin C according to the CKD-EPI Creatinine-Cystatin C equation adjusted for age, sex, and race (eGFRcr-cys). Nondiabetic CKD patients with arterial stiffness (baPWV ?1400?cm/s) showed higher GA levels than those without arterial stiffness (14.2 [8.7-20.2]% vs 13.0 [8.8-18.9]%, P?=?0.004). In the subgroup analysis, the patients who had both a higher GA level and a lower eGFRcr-cys, showed the highest baPWV compared with patients with a higher GA or a lower GFR alone. By Spearman's correlation analysis, GA correlated significantly with baPWV (r?=?+0.291, P?=?0.001) and fasting serum glucose level (r?=?+0.191, P?=?0.030), whereas The homeostatic model assessment of insulin resistance did not show any significant correlation with baPWV. Systolic blood pressure (r?=?+0.401 P?<?0.001), age (r?=?+0.574, P?<?0.001), high-density lipoprotein (HDL)-cholesterol level (r?=?-0.317, P?<?0.001), and eGFRcr-cys (r?=?-0.285, P?=?0.002) had a significant correlation with baPWV. According to multivariable logistic regression analysis, higher GA and systolic blood pressure were the independent risk factors affecting arterial stiffness. Our results suggest that serum GA is a potential risk factor of arterial stiffness in nondiabetic CKD patients.

Project description:BackgroundEffect of prediabetes and normal glucose on arterial stiffness remains controversial. The primary aim of this study was to investigate the relationship of fasting plasma glucose (FPG), postprandial glucose (PG) and glycosylated haemoglobin (HbA1c) with brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) in Caucasian adults. The secondary aim was to analyse this relationship by glycaemic status.MethodsCross-sectional study. Setting: Primary care. Participants: 2,233 subjects, 35-74 years. Measures: FPG (mg/dL) and HbA1c (%) of all subjects were measured using standard automated enzymatic methods. PG (mg/dL) was self-measured at home two hours after meals (breakfast, lunch and dinner) for one day using an Accu-chek ® glucometer. CAVI was measured using a VaSera VS-1500® device (Fukuda Denshi), and baPWV was calculated using a validated equation.ResultsCAVI and baPWV values were significantly higher in subjects with diabetes mellitus than in glucose normal and prediabetes groups (p<0.001). FPG, PG and HbA1c were positively associated with CAVI and baPWV. The β regression coefficient for: HbA1c was 0.112 (CI 95% 0.068 to 0.155) with CAVI, 0.266 (CI 95% 0.172 to 0.359) with baPWV; for PG was 0.006 (CI 95% 0.004 to 0.009 and for FPG was 0.005 (CI 95% 0.002 to 0.008) with baPWV; and for PG was 0.002 (CI 95% 0.001 to 0.003) and 0.003 (CI 95% 0.002 to 0.004) with CAVI (p<0.01 in all cases). When analysing by hyperglycaemic status, FPG, PG and HbA1c were positively associated with CAVI and baPWV in subjects with type 2 diabetes mellitus.ConclusionFPG, PG and HbA1c show a positive association with CAVI and baPWV, in Caucasian adults with intermediate cardiovascular risk factors. When analysing by hyperglycaemic status, the association is only maintained in subjects with type 2 diabetes mellitus.Trial registrationClinical Trials.gov Identifier: NCT01428934. Registered 2 September 2011. Retrospectively registered. Last updated September 8, 2016.

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Genetic variation in CYP17A1 is associated with arterial stiffness in diabetic subjects.

Publications

Genetic variation in CYP17A1 is associated with arterial stiffness in diabetic subjects.

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