RT Journal Article
T1 Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease
A1 Salas Ellacuriaga, Antonio
A1 Fachal Vilar, Laura
A1 Marcos Alonso, Sonia
A1 Vega Gliemmo, Ana Paula
A1 Martinón Torres, Federico
A1 Grupo de investigación ESIGEM (Estudio Sobre la Influencia Genética en la Enfermedad Meningocócica), 
AB Background and Aims: Meningococcal disease remains one of the most important infectious causes of death inindustrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are theresult of complex host genetics and environmental interactions. We investigated whether mitochondrial geneticbackground contributes to meningococcal disease (MD) susceptibility.Methodology/Principal Findings: Prospective controlled study was performed through a national research network on MDthat includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series ofMD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2[N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs(mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informativemarkers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples ofknown African, Native American and European ancestry (N = 711) were used as classification sets for the determination ofancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses(including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating aEuropean membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested anoverrepresentation of the synonym mtSNP G11719A variant (Pearson’s chi-square test; adjusted P-value = 0.0188; OR [95%CI] = 1.63 [1.22–2.18]). When cases were compared with CG2, the positive association could not be replicated. No positiveassociation has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and severalclinical variants.Conclusions: We did not find evidence of association between mtSNPs and mtDNA hgs with MD after carefully monitoringthe confounding effect of population sub-structure. MtDNA variability is particularly stratified in human populations owingto its low effective population size in comparison with autosomal markers and therefore, special care should be taken in theinterpretation of seeming signals of positive associations in mtDNA case-control association studies.
PB PLOS
YR 2009
FD 2009
LK http://hdl.handle.net/10347/22895
UL http://hdl.handle.net/10347/22895
LA eng
NO Salas A, Fachal L, Marcos-Alonso S, Vega A, Martinón-Torres F, Grupo de investigación ESIGEM (Estudio Sobre la Influencia Genética en la Enfermedad Meningocócica) (2009) Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease. PLoS ONE 4(12): e8347. https://doi.org/10.1371/journal.pone.0008347
NO The present project and the ESIGEM research group were supported by grants from Xunta de Galicia (PGIDIT06PXIB208079PR and Grupos Emerxentes: 2008/037), Fundación de Investigación Médica Mutua Madrileña (2008/CL444) and Ministerio de Ciencia e Innovación (SAF2008-02971) given to AS; Instituto Carlos III (Intensificación de la actividad investigadora) given to AVG; Consellería de Sanidade (Xunta de Galicia, RHI07/2-intensificación actividad investigadora), Instituto Carlos III (Intensificación de la actividad investigadora), and Convenio de colaboración de investigación (Wyeth España-Fundación IDICHUS), Fondo de Investigación Sanitaria (FIS; PI070069) del plan nacional de I+D+I and ‘fondos FEDER’ given to FMT
DS Minerva
RD 24 abr 2026