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CISH Variants Associated With Infectious Diseases

Variants linked to bacteremia, tuberculosis, malaria; having one variant ups risk by 18 percent

WEDNESDAY, May 19 (HealthDay News) -- Five single-nucleotide polymorphisms in the cytokine-inducible SRC homology 2 (SH2) domain protein (CISH) are associated with greater susceptibility to bacteremia, tuberculosis (TB) and malaria, according to research published online May 19 in the New England Journal of Medicine.

Chiea C. Khor, MB, BS, DPhil, of the Genome Institute of Singapore, and colleagues analyzed data from 8,402 people from Gambia, Hong Kong, Kenya, Malawi, and Vietnam participating in case-control series concerning bacteremia, TB and malaria. CISH appears critical for T-cell proliferation and survival following infection, the authors write.

The researchers found an association between CISH genetic variants and susceptibility to these diseases. People with one CISH risk allele had an 18 percent higher overall risk of one of these diseases, and the risk increased to 81 percent in people with four or more risk alleles.

"Our findings implicate CISH in multiple-pathogen susceptibility and raise the possibility that pharmacologic manipulation of the SOCS (suppressor of cytokine signaling) pathway may have an effect on the treatment of multiple, diverse infectious diseases. CISH variants may also influence responses to existing immunotherapies such as interleukin-2 therapy in renal-cell cancer, which is associated with wide and largely unexplained variations in interindividual response rates," the authors write.

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