Research Article: Angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to Kawasaki disease: a meta-analysis

Date Published: December , 2017

Publisher: Makerere Medical School

Author(s): Yan Pan, Hongzhu Lu.

http://doi.org/10.4314/ahs.v17i4.6

Abstract

The angiotensin-converting enzyme (ACE) I/D polymorphism has been reported to
be associated with Kawasaki disease (KD), but studies to date present
conflicting results.

The aim of this study is to derive a more precise estimation of the
association between the ACE I/D polymorphism and KD risk.

PubMed, EMBASE, CNKI and Wangfang databases were retrievaled to identify for
relevant studies from inception to May 2017. Pooled odds ratios (OR) with
95% confidence intervals (CI) were calculated using Stata 12.0 software.

A total of 6 case-control studies comprising 634 patients and 458 controls
were included in the meta-analysis, and we found a significant association
between the ACE I/D polymorphism and KD risk (D vs I:OR = 0.81, 95%CI =
0.31–2.11;DD vs II: OR = 1.03, 95%CI = 0.42–2.54; DI vs II:
OR = 1.44, 95%CI = 1.09–1.90; dominant model: OR = 1.43, 95%CI =
1.11–1.85; recessive model: OR = 1.21, 95%CI = 0.44–3.29 ).
When stratified by sample size>200, this polymorphism is associated
with an increased the risk of KD.

The I/D polymorphism in the ACE gene may be associated with susceptibility to
KD.

Partial Text

Kawasaki disease (KD) is an self-limited vasculitis that mainly affects young
children1. Although KD was first described
in 19672, its etiology is still not fully
understood. The clinical manifestations of KD include persistent fever, non-purulent
conjunctivitis, diffuse mucosal inflammation, polymorphous skin rashes, indurative
angioedema of the hands and feet, and non-suppurative cervical lymphadenopathy3. In about 20% of patients vasculitis will lead
to coronary artery lesions as detected by echocardiography, showing this to be the
principal cause of acquired heart disease of children4. Recent studies suggest that gene polymorphisms maybe associated with
KD, such as the FCGR2A gene rs1801274 polymorphism5.

Fisher’s exact test was used to test HWE for distributions of genotypes among
controls. The strength of the correlation between ACE I/D polymorphism and
susceptibility to KD was estimated by odds ratio (OR) and 95% confidence interval
(95%CI) as follows: D vs I, a homozygote comparison (DD vs II), a heterozygote
comparison (DI vs II), a dominant model (DD+DI vs II) and a recessive model (II+DI
vs DD) between groups. The heterogeneity among these articles was checked via the I2
test. When I2 > 50% indicated heterogeneity across studies, the random
effects model was used, otherwise the fixed effects model was performed. The
sensitivity analysis was performed by used via omitting each individual article, and
an individual article was suspected of excessive sensitivity if the point estimate
of its omitted analysis was outside the 95% CI of the pooled analysis. To assess the
potential publication bias, Begg’s and Egger’s tests were performed.
All statistical tests were performed with STATA (version 12.0; Stata Corporation,
College Station, TX).

Although the morbidity is highest in Asians, KD is a major cause of acquired heart
disease throughout the world18. After much
investigation, the pathogenesis of KD is still not yet well understood. ACE not only
increases vascular smooth muscle cell contraction, but also affects smooth muscle
proliferation, monocyte adhesion, platelet adhesion, and aggregation19,20. To date,
many studies have attempted to analyze the association between ACE I/D polymorphism
and KD susceptibility, but the results have been are inconsistent. The aim of this
meta-analysis was to investigate the possible association between ACE I/D
polymorphism and KD risk based on relevant studies.

Our pooled data showed a significant association between the ACE I/D polymorphism and
the risk of KD. Due to the defect limitations of the included research, future
large-scale investigations with appropriate design are required to confirm
association.

 

Source:

http://doi.org/10.4314/ahs.v17i4.6

 

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