Celiac.com 03/07/2011 - Although the HLA-DQ locus is clearly the strongest genetic factor influencing the development of celiac disease, it is certainly possible that other genes play supporting roles. Identifying these genes could help shed light on why certain genetically susceptible individuals develop celiac while others can happily (and healthily) eat gluten.
They sequenced the DNA of 504 unrelated Italian children and adolescents with celiac disease and 256 healthy controls. They were looking for two particular polymorphisms in each gene, as these were already known to be associated with immune disorders. They did find differences in the frequency of the different individual alleles between celiac patients and controls, but these differences did not reach the levels of statistical significance. The combination of both NALP1 variants together, however, was significantly more common in study participants with celiac.
NALP1 and NALP3 assemble the inflammasome by inciting the expression of the proinflammatory cytokine interleukin-1Î² , which in turn promotes autoreactive T cell function. The authors suggest that perhaps people with altered levels of responsiveness to interleukin-1Î² might be predisposed to autoimmunity. More work is needed to elucidate the role these NALP proteins might play in the intestinal damage that occurs in celiac disease.