Abstract
BackgroundConnective tissue growth factor (CTGF) has been implicated in the cardiac and kidney complications of type 2 diabetes, and the CTGF −945 G/C polymorphism is associated with susceptibility to systemic sclerosis, a disease characterised by tissue fibrosis. This study investigated the association of the CTGF −945 G/C promoter variant with cardiac complications (left ventricular (LV) hypertrophy (LVH), diastolic and systolic dysfunction) and chronic kidney disease (CKD) in type 2 diabetes.MethodsThe CTGF −945 G/C polymorphism (rs6918698) was examined in 495 Caucasian subjects with type 2 diabetes. Cardiac structure and function were assessed by transthoracic echocardiography. Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albuminuria, and CKD defined as the presence of kidney damage (decreased kidney function (eGFR <60 ml/min/1.73 m2) or albuminuria).ResultsThe mean age ± SD of the cohort was 62 ± 14 years, with a body mass index (BMI) of 31 ± 6 kg/m2 and median diabetes duration of 11 years [25th, 75th interquartile range; 5, 18]. An abnormal echocardiogram was present in 73% of subjects; of these, 8% had LVH alone, 74% had diastolic dysfunction and 18% had systolic ± diastolic dysfunction. CKD was present in 42% of subjects. There were no significant associations between the CTGF −945 G/C polymorphism and echocardiographic parameters of LV mass or cardiac function, or kidney function both before and after adjustment for covariates of age, gender, BMI, blood pressure and hypertension. CTGF −945 genotypes were not associated with the cardiac complications of LVH, diastolic or systolic dysfunction, nor with CKD.ConclusionsIn Caucasians with type 2 diabetes, genetic variation in the CTGF −945 G/C polymorphism is not associated with cardiac or kidney complications.
Highlights
Connective tissue growth factor (CTGF) has been implicated in the cardiac and kidney complications of type 2 diabetes, and the CTGF −945 G/C polymorphism is associated with susceptibility to systemic sclerosis, a disease characterised by tissue fibrosis
Cardiac and kidney complications are common in type 2 diabetes, but to date there are limited studies examining the role of CTGF in cardiac or kidney disease in these patients
We examined the relevance of the CTFG −945 G/ C promoter polymorphism to the cardiac complications of left ventricular hypertrophy (LVH), diastolic and systolic dysfunction, and kidney disease assessed with the estimated glomerular filtration rate and 24-hr urinary albumin excretion rate in a cohort of Caucasian subjects with type 2 diabetes
Summary
Research design and methods Study sample Ethical approval was obtained from the Human Research Ethics Committee at Austin Health, Melbourne and participants provided consent. The study included 495 subjects with type 2 diabetes, prospectively recruited at attendance for transthoracic echocardiography as part of a complications surveillance program at Austin Health, Melbourne, Australia as previously described [13,23]. Medical history and clinical measurements Subjects completed a questionnaire at the time of the echocardiogram, and information on diabetes duration, history of hypertension and ethnic background were obtained. Normality was assessed by evaluating quantile-quantile (Q-Q) plots for continuous variables and all Q-Q plots were normal, except for diabetes duration, 24-hr urinary albumin excretion and the E/eratio. The relationship between the CTGF −945 G/C polymorphism with continuous variables was examined by univariate general linear model analysis using the additive genetic model. The association of CTGF −945 G/C genotypes with continuous variables were examined further using multiple linear regression analysis after adjusting for covariates in the additive genetic model.
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