Inflammatory bowel disease (IBD) is characterised by an imbalance between prooxidant and anti-oxidant mechanisms. Cellular detoxification systems in IBD seem unable to adequately control the amplified generation of reactive oxygen species, put a stop to free radical injury and repair damaged cellular elements, suggesting that an increase in oxidative stress might be involved in the pathogenesis of IBD, 1 2 although the underlying molecular mechanisms remain largely undefined. Human paraoxonase family members (PON1, PON2, PON3) possess antioxidant and anti-inflammatory properties. 3–5 Despite the large impact of genetic variation on PON activity, its important role in controlling oxidative stress and inflammation, 5–8 as well as its association with several pathophysiological conditions, 4 no information is available on the relationship between PON genetic variants and IBD. Here, we wanted to assess whether the genotype or haplotype distribution of PON polymorphisms was different in patients with IBD during childhood compared with healthy controls. Eight common variants in PON1, PON2 and PON3 were genotyped by polymerase chain reaction allele-specific oligonucleotide hybridisation assays in 192 incident cases of childhood IBD (mean SD age of onset 11.03 (3.9) years) diagnosed and treated at Ste-Justine Hospital (Montreal, Ontario, Canada) and in 92 controls, all of French-Canadian origin. In PON1, three promoter polymorphisms (–107 CRT,–824 ARG and–907 CRG) and two coding polymorphisms (L55M and Q192R) were genotyped. Although their distribution did not differ significantly between patients with IBD and controls, overall the frequency of the 192R (ex6+ 78G) allele that seems to alter the structure of PON1 and influence enzyme activity in a substrate-dependent manner9 was consistently higher in patients with Crohn’s disease (table 1). The structures of 11 haplotypes in French-Canadians, including seven with a frequency. 7%, were inferred from the genotypic frequencies of the five PON1 variants (table 2). No significant differences were observed in the distribution of common haplotypes between patients with IBD and controls. The assessment of two linked PON2 polymorphisms (A148G and S311C) showed that people homozygous for 148GG and 311CC were less frequently found in patients with IBD than in controls (52% v 69%) suggesting a protective effect (odds ratio 0.5, 95% confidence interval 0.3 to 0.8, p= 0.011) against childhood IBD (table 3). No difference was observed in the frequency of PON2 variants in relation to the patient’s characteristics (data not shown). The physiological role of PON2 is still unknown, but it was suggested that it may exert its anti-oxidant role by decreasing intracellular oxidative stress. 5 Hence, it is plausible that subsequent to exposure to toxic

Competing interests: None. doi: 10.1136/gut. 2006.105627