The CTLA4 variants may interact with the IL23R- and NOD2-conferred risk in development of Crohn's disease

BMC Medical Genetics

Table 4 Stratified analysis of the effect conferred by the CTLA4 CT60, JO31 and JO27-1 variants

NOD2stratum defined using the Leu1007fsX1008 polymorphism ¹⁾	CT60 (rs3087243), A carriage rate (genotypes A/G, A/A)	JO31 (rs11571302), T carriage rate (genotypes G/T, T/T)	JO27-1 (rs11571297), G carriage rate (genotypes A/G, G/G)	Haplotype "ATG" ⁴
*NOD2*"+"
cases, n = 108	67 (62%)	69 (64%)	70 (65%)
controls, n = 48	38 (79%)	40 (83%)	42 (88%)
OR (95%CI) ²⁾	0.43 (0.19-0.95)	0.35 (0.15-0.83)	0.26 (0.1-0.68)	0.62 (0.37 - 1.05)
*NOD2* "wt/wt"
cases, n = 224	157 (70%)	166 (74%)	168 (75%)
controls, n = 434	277 (64%)	292 (67%)	294 (68%)
OR (95%CI) ²⁾	1.33 (0.94-1.88)	1.37 (0.96-1.96)	1.42 (0.99-2.03)	1.21 (0.96. - 1.53)
Heterogeneity between *NOD2* -defined strata ³⁾	p = 0.011	p = 0.0042	p = 0.0011	p = 0.043

Strata of the risk conferred by the p.Leu1007fsX1008 polymorphism of the NOD2 gene: the effect of CTLA4 is apparent in the stratum with an increased NOD2-associated risk
1) NOD2 "+": homozygous or heterozygous for the minor allele at the p.Leu1007fsX1008 polymorphism; NOD2 "wt/wt": wild-type homozygote at the p.Leu1007fsX1008 polymorphism. The NOD2 "+" category is associated with an increased risk of OR = 4.36, 95%CI 2.95 - 6.49 as compared to "wt/wt" category.
2) OR for the effect of the polymorphism in the specific stratum (NOD2"+" and NOD2"wt/wt"), adjusted for the effect of the IL23R p.381Gln variant and p.Gly908Arg, p.Arg702Trp in the NOD2 gene. Results significant at p < 0.05 are in bold.
3) Heterogeneity in the effect conferred by the CTLA4 polymorphisms was assessed between NOD2-defined strata using the Mantel-Haenszel test of homogeneity.
4) The implemented expectation-maximization algorithm did not allow individual imputation and counting of haplotypes.

ISSN: 1471-2350