| Summary: | Gulf War illness (GWI) encompasses a constellation of persistent debilitating symptoms associated with significant changes in central nervous system (CNS) and immune functioning. Currently, there is no validated biomarker for GWI risk susceptibility. Given the impact of immune responses linked to GWI symptomology, genetic variability that causes persistent inflammatory/immune alterations may be key. This Boston University-based Gulf War Illness Consortium (GWIC) study investigated the impact of single nucleotide polymorphisms (SNPs) in variants of immune and pain genetic markers <i>IL1B</i>, <i>IL2</i>, <i>IL6</i>, <i>IL6R</i>, <i>IL10</i>, <i>TNF</i>, <i>TGF</i>, <i>TLR2</i>, <i>TLR4</i>, <i>MD2</i>, <i>MYD88</i>, <i>BDNF</i>, <i>CRP</i>, <i>ICE, COMT</i> and <i>OPRM1</i> on GWI occurrence in a Caucasian subset of Gulf War (GW) veterans with (cases, <i>n</i> = 170) and without (controls, <i>n</i> = 34) GWI. Logistic regression modeling created a prediction model of GWI risk that associated genetic variability in <i>TGF</i> (rs1800469, <i>p</i> = 0.009), <i>IL6R</i> (rs8192284, <i>p</i> = 0.004) and <i>TLR4</i> (rs4986791, <i>p</i> = 0.013) with GWI occurrence. This prediction model was specific and sensitive, with a receiver operator characteristic area under the curve of 71.4%. This is the first report of immune genetic variability being predictive of GWI and warrants validation in larger independent cohorts. Future reports will present interactions of these genetic risk factors with other characteristics of GW service.
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