NOD2 Sequencing in Iranian Children with Crohn’s Disease

Zusammenfassung

Morbus Crohn (MC) ist eine chronisch entzündliche Erkrankung des Verdauungstrakts. Die genaue Ätiologie der Erkrankung ist zwar immer noch unbekannt, aber mehrere Studien haben in Assoziation mit MC über Mutationen im CARD15/NOD2-Gen berichtet. Die vorliegende Studie wurde durchgeführt, um herauszufinden, ob das CARD15/NOD2-Gen pädiatrische Patienten im Iran zu MC prädisponiert. Alle 12 kodierenden Exons des CARD15/NOD2-Gens wurden bei 16 Crohn-Patienten mit Krankheitsbeginn im Kindesalter sequenziert. Die Sequenzierung des CARD15/NOD2-Gens ergab keine Mutationen. Zwei Patienten hatten jedoch einen Polymorphismus in diesem Gen. Bei einem 10-jährigen Mädchen mit mild verlaufendem MC, das eine rektovaginale und perianale Fistel und multiple Marisken hatte, wurde der heterozygote SNP (Single Nucleotide Polymorphism) rs3135500 C > Y im Exon 12.3 gezeigt. Ein 5-jähriger Junge mit moderatem bis schwerem MC sowie einer Anamnese von perianalen Fissuren und oraler Candidiasis hatte einen heterozygoten SNP in den Exons 4.1 and 12.1. Die Ergebnisse dieser Studie zeigen, dass CARD15/NOD2-Mutationen bei iranischen Patienten mit MC-Beginn im Kindesalter nicht für die Pathogenese der Erkrankung verantwortlich sind.

Abstract

Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Although the exact etiology of disease is still unknown, mutations in the CARD15/NOD2 gene have been reported in association with CD in several studies. This study was performed to determine whether the CARD15/NOD2 gene confers susceptibility to Iranian pediatric patients with CD. All 12 coding exons of the CARD15/NOD2 gene were sequenced in 16 enrolled pediatric onset CD patients. Sequencing of the CARD15/NOD2 gene showed no mutation. However, two patients harbored polymorphisms within this gene. A heterozygous single nucleotide polymorphism rs3135500 C > Y in the exon 12.3 was detected in a 10-year-old girl with mild severity of CD and history of rectovaginal and perianal fistula, and multiple skin tags. The other 5-year-old boy with moderate to severe CD and a history of perianal fissures and oral candidiasis harbored heterozygous single nucleotide polymorphisms in exons 4.1 and 12.1. The results of the present study show that the CARD15/NOD2 mutations in Iranian patients with pediatric onset CD are not responsible for the pathogenesis of disease.

Key words

Crohn’s disease - mutation - NOD2 - polymorphism

Schlüsselwörter

Morbus Crohn - Mutationen - NOD2 - Polymorphismus

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