Identification of polymorphisms of the IκBα gene associated with an increased risk of multiple myeloma

Abstract When NF-κB proteins are bound to IκBα , they remain in the cytosol, and are unable to act as transcription factors. Phosphorylation of IκBα at Serine32 and Serine36 has been shown to stimulate ubiquitination followed by proteasome-mediated degradation of IκBα , resulting in the release of active NF-κB . NF-κB activity is associated with bone loss and B cell growth as well as chemotherapy resistance. Because previous studies have shown abnormalities of the IκBα gene in patients with lymphoma, we determined whether alterations of this gene also occur in multiple myeloma (MM). We determined the DNA sequence of the IκBα gene from bone marrow mononuclear cells from 18 MM patients and 24 healthy subjects as well as two MM cell-lines. We identified eight polymorphisms. Statistically, the prevalence of three polymorphisms, one in exon 1 and two in exon 6, were significantly higher in MM patients (α>1) compared with samples from control subjects. Six of eight polymorphisms in myeloma samples have also been identified in previous studies of IκBα sequences derived from lymphoma samples. In addition, we detected two polymorphisms in the IκBα gene that have not been previously reported. Together, these results provide the basis for future evaluation the IκBα/NF-κB pathway in MM patients.