Association of CD40 SNPs with Moyamoya in a Chinese children population

Abstract

Background: The etiology of Moyamoya disease (MMD) remains unknown to a large extent. Immune and inflammation dysfunction may play a role in the pathogenesis of this rare disease. Coexisting Kawasaki disease (KD) with MMD were reported and both diseases have a feature of vasculopathy, raising the hypothesis that there may be some common pathologic factors. We investigated single nucleotide polymorphisms (SNPs) previously identified in KD and performed a genetic analysis among Chinese pediatric patients with MMD.

Results: We analyzed patients’ DNA for the SNPs in B lymphoid tyrosine kinase, CD40, and coatomer protein complex beta-2 subunit, which had been associated with KD by literatures. Genotyping was performed by sequencing the genetic regions containing the SNPs with customized primers. A total of 5 genotype polymorphisms were examined among 48 pediatric MMD cases and 50 healthy controls. The mean age of MMD children was 6.72 ± 3.63 years old, while 7.31 ± 3.79 in controls. We found two SNPs of CD40 were associated with MMD. Polymorphisms rs4813003 major allele CC and rs1535045 minor allele TT were significantly higher in MMD cases. The other SNPs showed no statistical difference between MMD cases and controls.

Conclusions: Our findings provide evidence that there may be a relationship between MMD and auto-immune dysfunction. We hypothesize that these genetic features may lead to the pathogenesis within the vascular wall. Further study regarding whether CD40 can function as the personalized target of MMD should be investigated in future.

Keywords:

• CD40
• Single nucleotide polymorphism
• Children
• Moyamoya disease

Ethics approval and consent to participate

The protocol (2014-090) was approved by the Medical Ethics Committee of the Children’s Hospital of Fudan University.

Acknowledgements

The authors are grateful for the assistance of Dr. Guifa Xi from Development Biology Program, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. [email protected].

Disclosure statement

The authors declare that they have no competing interests.

Consent for publication

The guardians of the included patients consented the publication.

Availability of data and material

The datasets used and/or analyzed during the current study is available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the [Shanghai Health Bureau] under Grant [20144Y0056] and [National Natural Science Foundation of China] under Grant [81171082].