Background Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14–1.53)]. Conclusion Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.
Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain;Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain;Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain;Instituto de Parasitología y Biomedicina “López Neyra”, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain;Instituto de Parasitología y Biomedicina “López Neyra”, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain;Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain;Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain;Laboratorio de Investigación, Instituto de Neurociencias Clínicas, Hospital Regional Universitario, Málaga, Spain;Servicio de Neurología, Instituto de Neurociencias Clínicas, Hospital Regional Universitario, Málaga, Spain;Unidad de Esclerosis Múltiple, Hospital Virgen Macarena, Sevilla, Spain;Servicio de Neurología, Hospital de Basurto, Bilbao, Spain;Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain;Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain;Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain;Achucarro Basque Center for Neuroscience – UPV/EHU, Zamudio, Spain;IKERBASQUE, Basque Foundation for Science, Bilbao, Spain;Instituto de Parasitología y Biomedicina “López Neyra”, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain;Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
Recommended Citation:
Belén de la Hera,Jezabel Varadé,Marta García-Montojo,et al. Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis[J]. PLOS ONE,2014-01-01,9(3)