Dataset Information

Rare variants in MYD88, IRAK4 and IKBKG and susceptibility to invasive pneumococcal disease: a population-based case-control study.

ABSTRACT: Although rare variants within the Toll-like receptor signalling pathway genes have been found to underlie human primary immunodeficiencies associated with selective predisposition to invasive pneumococcal disease (IPD), the contribution of variants in these genes to IPD susceptibility at the population level remains unknown. Complete re-sequencing of IRAK4, MYD88 and IKBKG genes was undertaken in 164 IPD cases from the UK and 164 geographically-matched population-based controls. 233 single-nucleotide variants (SNVs) were identified, of which ten were in coding regions. Four rare coding variants were predicted to be deleterious, two variants in MYD88 and two in IRAK4. The predicted deleterious variants in MYD88 were observed as two heterozygote cases but not seen in controls. Frequencies of predicted deleterious IRAK4 SNVs were the same in cases and controls. Our findings suggest that rare, functional variants in MYD88, IRAK4 or IKBKG do not significantly contribute to IPD susceptibility in adults at the population level.

SUBMITTER: Ellis MK

PROVIDER: S-EPMC4401548 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Rare variants in MYD88, IRAK4 and IKBKG and susceptibility to invasive pneumococcal disease: a population-based case-control study.

Ellis Magda K MK Elliott Katherine S KS Rautanen Anna A Crook Derrick W DW Hill Adrian V S AV Chapman Stephen J SJ

PloS one 20150417 4

Although rare variants within the Toll-like receptor signalling pathway genes have been found to underlie human primary immunodeficiencies associated with selective predisposition to invasive pneumococcal disease (IPD), the contribution of variants in these genes to IPD susceptibility at the population level remains unknown. Complete re-sequencing of IRAK4, MYD88 and IKBKG genes was undertaken in 164 IPD cases from the UK and 164 geographically-matched population-based controls. 233 single-nucle ...[more]

PMID: 25886387

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Project description:BackgroundAlthough certain opioid analgesics have immunosuppressive properties and increase the risk for infections in animals, the clinical effects of prescription opioid use on infection risk among humans are unknown.ObjectiveTo test the hypothesis that prescription opioid use is an independent risk factor for invasive pneumococcal disease (IPD).DesignNested case-control study.SettingTennessee Medicaid database linked to Medicare and Active Bacterial Core surveillance system databases (1995 to 2014).Patients1233 case patients with IPD aged 5 years and older matched to 24 399 control participants by diagnosis date, age, and county of residence.MeasurementsOpioid use was measured on the basis of pharmacy prescription fills. Invasive pneumococcal disease was defined by the isolation of Streptococcus pneumoniae from a normally sterile site. The odds of current opioid use were compared between the case and control groups, accounting for known IPD risk factors. Secondary analyses categorized opioid use by opioid characteristics, applied an IPD risk score to assure comparability between exposure groups, and analyzed pneumonia and nonpneumonia IPD cases separately.ResultsPersons in the case group had greater odds than control participants of being current opioid users (adjusted odds ratio [aOR], 1.62 [95% CI, 1.36 to 1.92]). Associations were strongest for opioids that were long acting (aOR, 1.87 [CI, 1.24 to 2.82]), of high potency (aOR, 1.72 [CI, 1.32 to 2.25]), or were used at high dosages (50 to 90 morphine milligram equivalents [MME]/d: aOR, 1.71 [CI, 1.22 to 2.39]; ≥90 MME/d: aOR, 1.75 [CI, 1.33 to 2.29]). Results were consistent when the IPD risk score was taken into account and pneumonia and nonpneumonia IPD were analyzed separately.LimitationsUnmeasured confounding and measurement error, although sensitivity analyses suggested that neither was likely to affect results. Actual opioid use and other nonprescription use (such as illicit opioid use) were not measured.ConclusionOpioid use is associated with an increased risk for IPD and represents a novel risk factor for these diseases.Primary funding sourceNational Institutes of Health.

Dataset Information

Rare variants in MYD88, IRAK4 and IKBKG and susceptibility to invasive pneumococcal disease: a population-based case-control study.

Publications

Rare variants in MYD88, IRAK4 and IKBKG and susceptibility to invasive pneumococcal disease: a population-based case-control study.

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