Associations of Immune Genetic Variability with Gulf War Illness in 1990-1991 Gulf War Veterans from the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study.

Janet K Coller,Jonathan Tuke,Lea Steele,Kimberly Sullivan,Nancy Klimas,Maria Abreu,Emily Quinn,Kristina Aenlle,Taylor J Wain

doi:10.3390/brainsci11111410

Abstract

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 IL1B, IL2, IL6, IL6R, IL10, TNF, TGF, TLR2, TLR4, MD2, MYD88, BDNF, CRP, ICE, COMT and OPRM1 on GWI occurrence in a Caucasian subset of Gulf War (GW) veterans with (cases, n = 170) and without (controls, n = 34) GWI. Logistic regression modeling created a prediction model of GWI risk that associated genetic variability in TGF (rs1800469, p = 0.009), IL6R (rs8192284, p = 0.004) and TLR4 (rs4986791, p = 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.

Highlights

Introduction distributed under the terms andGulf War illness encompasses a constellation of persistent debilitating symptoms suffered by a third of the nearly 700,000 U.S soldiers who served in the 1990–1991 PersianGulf War (GW) [1]
There is mounting evidence demonstrating the importance of central nervous system (CNS) inflammatory markers and immune system activation in the development of chronic symptoms in GW veterans [6]
This suggests CNS neuro-immune signaling cells may have an important role in the development and sustained health symptom and cognitive decrements associated with Gulf War illness (GWI) [10]

Summary

Introduction

Introduction distributed under the terms andGulf War illness encompasses a constellation of persistent debilitating symptoms suffered by a third of the nearly 700,000 U.S soldiers who served in the 1990–1991 PersianGulf War (GW) [1]. There are studies showing lower white matter volumes and increased microstructural diffusivity on brain imaging in GW veterans exposed to neurotoxicants linked to increased health symptom complaints [3,4,7,8,9]. This suggests CNS neuro-immune signaling (glial) cells may have an important role in the development and sustained health symptom and cognitive decrements associated with GWI [10]. The CNS inflammatory response [14] induces sickness response symptoms including fatigue, muscle and joint pain and cognitive difficulties

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Results

Conclusion