NCF1 gene and pseudogene pattern: association with parasitic infection and autoimmunity

Abstract

Background: Neutrophil cytosolic factor 1, p47phox (NCF1) is a component of the leukocyte NADPH oxidase complex mediating formation of reactive oxygen intermediates (ROI) which play an important role in host defense and autoimmunity. An individual genomic pattern of ncf1 and its two types of pseudogenes (reflected by the DeltaGT/GTGT ratio) may influence the individual capacity to produce ROI.

Methods: NCF1DeltaGT/GTGT ratios were correlated with clinical parameters and ROI production during Plasmodium falciparum malaria and with susceptibility to the autoimmune disease multiple sclerosis (MS).

Results: Among Gabonese children with severe malaria, ROI production from peripheral blood tended to be higher in individuals with a DeltaGT/GTGT ratio </= 1:1. DeltaGT/GTGT ratios were not associated with susceptibility to MS, but to age-of-onset among MS patients.

Conclusion: The genomic pattern of NCF1 and its pseudogenes might influence ROI production but only marginally influence susceptibility to and outcome of malaria and MS.

Figure 1

Maximum basal (left) and PMA-stimulated (right) ROI production in whole blood preparations of children suffering from severe malaria. Individuals with a ΔGT/GTGT ratio of 2:1 have two type I ΨNCF1 genes per NCF1 gene while individuals with a ratio of 1:1 or 1:2 have presumably one or more type II ΨNCF1 genes per NCF1 gene. Shown are log-transformed maximum ROI levels measured during a 30-minute period, triangles represent individual data points, horizontal lines indicate means. For statistical analysis see text.

Figure 2

Frequency of individuals with a ≤ 1:1 ΔGT/GTGT ratio among MS patients and control persons from Germany and Poland. The combined odds ratio for association of the ratio ≤ 1:1 with MS among German and Polish patients was calculated using revman software (version 4.2 for Windows, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2003).

Figure 3

Age-of-onset among German MS patients (bout onset only) with different ΔGT/GTGT ratios. Triangles represent individual data points of 41 MS patients with a ΔGT/GTGT ratio ≤ 1:1 and 161 MS patients with a ΔGT/GTGT ratio ≥ 2:1, horizontal lines indicate means. For statistical analysis see text.