Interplay between NOD1 polymorphisms and gene expression in the pathogenesis of gallstone disease.

BACKGROUND: Gallstone disease (GSD) is a multifactorial disorder with both genetic and inflammatory influences. Nucleotide-binding oligomerization domain containing protein 1 (NOD1) has an important role in innate immunity and in regulation of gut microbiota and its genetic relationship to GSD is unknown. AIM: To explore the association of NOD1 gene polymorphism (rs5743336 and rs6958571) and gene expression with gallstone disease. METHODS: A case-control study was carried out with ultrasound diagnosed gallstone patient and age and sex matched controls. Genotyping of rs5743336 and rs6958571 was done by PCR-RFLP. NOD1 mRNA expression was measured by qRT-PCR. Statistical analysis comprised comparisons of genotype and allele frequencies and logistic regression under various genetic models was performed. RESULTS: The rs5743336 (GG) genotype was significantly less common in cases than in controls, suggesting a protective effect against GSD (p < 0.05). No significant association was found for rs6958571. In addition, NOD1 expression levels were significantly lower in GSD cases than controls (fold change = 0.415443; p-value = 0.038407) and impaired microbial sensitivity may contribute to gallstone pathogenesis. CONCLUSION: This is the first study to find an association between NOD1 genetic variation and gallstone disease. The GG genotype of rs5743336 is protective, and decreased NOD1 expression could be a factor in the development of disease.