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European Journal of Pediatrics

, Volume 176, Issue 8, pp 1035–1045 | Cite as

Inducible nitric oxide synthase gene polymorphisms are associated with a risk of nephritis in Henoch-Schönlein purpura children

  • Jue Jiang
  • Wuqiong Duan
  • Xu Shang
  • Hua Wang
  • Ya Gao
  • Peijun TianEmail author
  • Qi ZhouEmail author
Original Article

Abstract

Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children, and HSP nephritis (HSPN) is a major complication of HSP and is the primary cause of morbidity and mortality. Previous studies have suggested that inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of HSP. In this study, we performed a detailed analysis to investigate the potential association between iNOS polymorphisms and the risk of HSP and the tendency for children with HSP to develop HSPN in a Chinese Han population. A promoter pentanucleotide repeat (CCTTT)n and 10 functional single-nucleotide polymorphisms (SNPs) from 532 healthy controls and 513 children with HSP were genotyped using the MassARRAY system and GeneScan. The results suggested that the allelic and genotypic frequencies of the rs3729508 polymorphism were nominally associated with susceptibility to HSP. In addition, there was a significant difference in the allelic distribution of the (CCTTT)12 repeats and rs2297518 between the HSP children with and without nephritis; the HSP children with nephritis exhibited a significantly higher frequency of the (CCTTT)12 repeats and A allele of rs2297518 than the HSP children without nephritis (P FDR = 0.033, OR = 1.624, 95% CI = 1.177–2.241 and P FDR = 0.030, OR = 1.660, 95% CI = 1.187–2.321, respectively).

Conclusion: Our results support that iNOS polymorphisms are associated with the risk of HSP and may strongly contribute to the genetic basis of individual differences in the progression to nephritis among children with HSP in the Chinese Han population.

What is Known:

The etiology of HSP is unknown, but the genetic factors may play an important role in the pathogenesis of HSP.

iNOS could contribute to the development and clinical manifestations of HSP, and this has not been studied extensively so far.

What is New:

Our results support that iNOS polymorphisms not only are associated with HSP risk but also strongly contribute to the genetic basis of individual differences in the progression of HSP to nephritis among Chinese Han children.

Keywords

Henoch-Schönlein purpura Henoch-Schönlein purpura nephritis Inducible nitric oxide synthase Single nucleotide polymorphisms Chinese Han population 

Abbreviations

CHB

Population Han Chinese in Beijing

CI

Confidence interval

eNOS

Endothelial nitric oxide synthase

HSP

Henoch-Schönlein purpura

HSPN

HSP nephritis

HWE

Hardy-Weinberg equilibrium

iNOS

Inducible nitric oxide synthase

LD

Linkage disequilibrium

MAF

Minor allele frequency

nNOS

Neuronal nitric oxide synthases

NO

Nitric oxide

OR

Odds ratio

SNP

Single-nucleotide polymorphisms

STR

Short tandem repeat

UTR

Untranslated region

Notes

Acknowledgements

We are thankful to all of the children who participated in this study and thank all of the doctors and nurses at our hospital for collecting the specimens and clinical information. We want to thank Dr. Erdi Xu for her help with the study design and manuscript writing.

Authors’ contributions

Conceived and designed the experiments: JJ PT QZ. Performed the experiments: WD XS HW. Analyzed the data: WD YG. Contributed reagents/materials/analysis tools: WD PT. Wrote the paper: JJ PT QZ.

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Children whose parents gave informed written consent were recruited.

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of UltrasoundThe Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Department of PediatricsAnkang Center HospitalAnkangPeople’s Republic of China

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