Addition of host genetic variants in a prediction rule for post meningitis hearing loss in childhood: a model updating study

Abstract

BackgroundSensorineural hearing loss is the most common sequela in survivors of bacterial meningitis (BM). In the past we developed a validated prediction model to identify children at risk for post-meningitis hearing loss. It is known that host genetic variations, besides clinical factors, contribute to severity and outcome of BM. In this study it was determined whether host genetic risk factors improve the predictive abilities of an existing model regarding hearing loss after childhood BM.MethodsFour hundred and seventy-one Dutch Caucasian childhood BM were genotyped for 11 single nucleotide polymorphisms (SNPs) in seven different genes involved in pathogen recognition. Genetic data were added to the original clinical prediction model and performance of new models was compared to the original model by likelihood ratio tests and the area under the curve (AUC) of the receiver operating characteristic curves.ResultsAddition of TLR9-1237 SNPs and the combination of TLR2 + 2477 and TLR4 + 896 SNPs improved the clinical prediction model, but not significantly (increase of AUC’s from 0.856 to 0.861 and from 0.856 to 0.875 (p = 0.570 and 0.335, respectively). Other SNPs analysed were not linked to hearing loss.ConclusionsAlthough addition of genetic risk factors did not significantly improve the clinical prediction model for post-meningitis hearing loss, AUC’s of the pre-existing model remain high after addition of genetic factors. Future studies should evaluate whether more combinations of SNPs in larger cohorts has an additional value to the existing prediction model for post meningitis hearing loss.

NOD1 in contrast to NOD2 functional polymorphism influence Chlamydia trachomatis infection and the risk of tubal factor infertility

“…More work in this field, however, still has to be done. A study by Sanders and colleagues (2013) increased the predictive capacities of a post-meningitis hearing loss prediction model by adding a number of single nucleotide polymorphisms (SNPs) in different PRR genes (Sanders et al, 2013). Women carrying two or more SNPs in PRR genes involved in recognizing that C. trachomatis show more than 2-fold higher risk of developing tubal pathology after C. trachomatis infection compared to women with less than two PRR SNPs (den Hartog et al, 2006).…”

The Potential Role for Host Genetic Profiling in Screening for Chlamydia-Associated Tubal Factor Infertility (TFI)—New Perspectives

“…Moreover, assessing the introduction of similar technologies gives insight into potential outcomes. Sanders and colleagues managed to—albeit modestly—increase the PPV of a post-meningitis hearing loss prediction model for children by adding a palette of SNPs in innate immunity genes [58]. Genetic risk models typically do not outperform clinical models, but what must be taken into consideration is the significance of well-defined study populations and proper stratification, which is frequently lacking in these studies [59,60].…”

Study protocol: The Dutch 20|30 Postmeningitis study: a cross-sectional follow-up of two historical childhood bacterial meningitis cohorts on long-term outcomes

“…A total of 471 patients (70%) returned a buccal swab. The methodology used to construct these cohorts is extensively described in earlier published studies [12, 27, 28]. All patients from the original cohorts who consented to future follow-up studies will be invited for the present study.…”