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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e3181b7a6a4
Original Articles: Gastroenterology

Early-onset Crohn Disease Is Associated With Male Sex and a Polymorphism in the IL-6 Promoter

Sagiv-Friedgut, Keren*; Karban, Amir; Weiss, Batya; Shaoul, Ron§; Shamir, Raanan; Bujanover, Yoram; Reif, Shimon||; Boaz, Mona#; Shani, Inbar**; Levine, Arie*; Leshinsky-Silver, Esther**

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Aims: Pediatric onset of Crohn disease (CD) is characterized by male sex predominance while adult-onset disease demonstrates female sex predominance. It has been postulated that this phenomenon may be genetically determined or due to an effect of estrogen on age of onset. Interleukin (IL)-6 modulates the TH17 pathway, and the IL-6 promoter is modulated by estrogen, possibly linking genetically determined inflammation and the presence of estrogen. The aim of our study was to investigate whether differences in IL-6 promoter genotype could explain male sex in earlier disease onset.

Patients and Methods: We genotyped 333 patients with CD and 100 controls, 162 pediatric-onset patients (age of onset 18 years and younger) for the IL-6-174 polymorphic site. Genotype, sex, and age of onset were compared.

Results: Males with IL-6-174GG genotype (the wild-type allele) had an increased risk for a younger age of onset compared to males with IL-6-174GC or CC genotype (G → C genotype), hazard ratio (HR) 1.49, P = 0.02, 95% confidence interval (CI) 1.07–2.09. Females with GG genotype were not found to have an increased risk for a younger age of onset compared with females with G → C genotype, HR 1.01, P = 0.96, 95% CI 0.72–1.41.

Conclusions: Males with IL-6-174GG genotype are prone to develop CD at a younger age than males with the IL-6-174G → C genotype. Our study suggests that age of onset may be modified by the IL-6-174GG genotype and this modification is sex dependent. This may be due to increased transcription of IL-6, an effect that may be repressed by estrogen in females.

© 2010 Lippincott Williams & Wilkins, Inc.


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