Associations between microRNA (miR-21,126,155and 221),albuminuria and heavy metals in Hong Kong Chinese adolescents
Alice P.S.Kong a ,1,Kang Xiao a ,1,Kai Chow Choi b ,Gang Wang a ,Michael H.M.Chan c ,Chung Shun Ho c ,Iris Chan c ,Chun Kwok Wong c ,Juliana C.N.Chan a ,d ,Cheuk Chun Szeto a ,⁎
a
Department of Medicine and Therapeutics,The Chinese University of Hong Kong,Hong Kong SAR,China b
Nethersole School of Nursing,The Chinese University of Hong Kong,Hong Kong SAR,China c
Department of Chemical Pathology,The Chinese University of Hong Kong,Hong Kong SAR,China d
Li Ka Shing Institute of Health Sciences,The Chinese University of Hong Kong,Hong Kong SAR,China
a b s t r a c t
a r t i c l e i n f o Article history:
Received 9January 2012
Received in revised form 27January 2012Accepted 16February 2012Available online 1March 2012Keywords:Arsenic Lead
Cadmium Mercury Albuminuria Adolescents
Background and aim:Pathogenetic mechanisms underlying albuminuria are not completely understood.Heavy metals might lead to atherosclerosis and kidney damage.miR-21,126,155and 221regulated endothelial function and might contribute to the development of albuminuria.To date,no clinical trial has explored the relationship between miRNAs,microalbuminuria and heavy metals in human.In this study,we aimed to examine the association between microalbuminuria,miRNAs and heavy metals in adolescents.Materials and methods:From a cross-sectional,population-recruited study,we identi fied 60school children aged 12–19years with microalbuminuria (de fined as spot urine albumin –creatinine ratio >3.5mg/mmol).We compared the urine heavy metals (arsenic,mercury,cadmium and lead)and miRNAs levels (miR-21,126,155and 221)with another 60age-and sex-matched normoalbuminuric adolescents as control.Results:Mean age of the study cohort was 15.5±2.1years.43%were boys.Among the four miRNAs tested,only miR-21was associated with microalbuminuria (p =0.02).Urinary arsenic and lead levels had a negative association with both miR-21and miR-221.No signi ficant association was found between heavy metals examined and microalbuminuria.
Conclusion:The results of our study suggest an association between microalbuminuria,miR-21and heavy metals (arsenic and lead).This might imply that miR-21is involved in the pathogenetic mechanisms linking heavy metals exposure and albuminuria.
©2012Elsevier B.V.All rights reserved.
1.Introduction
Urbanization and technology have led to rapid global transition and may contribute to the pandemic of non-communicable diseases including cardiovascular diseases (CVD)and chronic kidney disease (CKD).Early identi fication of at-risk individuals is important to prevent progression of CVD and CKD.Albuminuria,a marker of vascular and renal damage,is a simple,commonly used biochemical tool to identify individuals at risk of development of CVD and CKD.
Apart from changes in habits and lifestyle,exposure to heavy metals is increasingly recognized as a consequence of urbanization.Most heavy metals cannot be metabolized by our body,and excessive accumulation in the body will disturb the normal functions of cells.
Kidney is the key organ to eliminate heavy metals from the body.Heavy metals might lead to albuminuria through inducing oxidative stress to renal tubular cells [1,2].Certain heavy metals have additive effect in inducing nephrotoxicity.For example,synergistic effect of arsenic (As)and cadmium (Cd)in causing renal damage has been demonstrated in Chinese general population [3].In addition,chronic exposure to toxic heavy metals may promote atherosclerosis and contribute to the development of CKD and CVD [2,4].
MicroRNAs (miRNAs)are endogenous,small non-coding RNAs which are involved in regulation of gene expression and many crucial biological processes,including development,differentiation,apoptosis,and proliferation [5].Four miRNAs,miR-21,miR-126,miR-155and miR-221,had been reported to have regulatory functions in gene expression of vascular proliferation factors such as programmed cell death protein 4(PDCD4),phosphatase and tensin(PTEN),vascular endothelial growth factor(VEGF),angiotensin II type 1receptor (AT 1R)and vascular smooth muscle cell (VSMC)[6–9].Whether these four miRNAs are involved in the pathogenetic processes of albuminuria through their roles in regulating gene expressions in vasculature have not been explored.It is plausible that heavy metals induced the
Clinica Chimica Acta 413(2012)1053–1057
⁎Corresponding author at:Department of Medicine and Therapeutics,The Chinese University of Hong Kong,Prince of Wales Hospital,Shatin,N.T.,Hong Kong SAR,China.Tel.:+852********;fax:+852********.
E-mail address:ccszeto@.hk (C.C.Szeto).1
APSK and KX:co-first author of the
manuscript.0009-8981/$–see front matter ©2012Elsevier B.V.All rights reserved.doi:
10.1016/a.2012.02.014
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