title: Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients.
abstract: BACKGROUND
  The genetic contribution to stroke is well established but it has proven difficult to identify the genes and the disease-associated alleles mediating this effect, possibly because only nuclear genes have been intensely investigated so far. Mitochondrial DNA (mtDNA) has been implicated in several disorders having stroke as one of its clinical manifestations. The aim of this case-control study was to assess the contribution of mtDNA polymorphisms and haplogroups to ischemic stroke risk.
  
  
  METHODS
  We genotyped 19 mtDNA single nucleotide polymorphisms (SNPs) defining the major European haplogroups in 534 ischemic stroke patients and 499 controls collected in Portugal, and tested their allelic and haplogroup association with ischemic stroke risk.
  
  
  RESULTS
  Haplogroup H1 was found to be significantly less frequent in stroke patients than in controls (OR = 0.61, 95% CI = 0.45-0.83, p = 0.001), when comparing each clade against all other haplogroups pooled together. Conversely, the pre-HV/HV and U mtDNA lineages emerge as potential genetic factors conferring risk for stroke (OR = 3.14, 95% CI = 1.41-7.01, p = 0.003, and OR = 2.87, 95% CI = 1.13-7.28, p = 0.021, respectively). SNPs m.3010G>A, m.7028C>T and m.11719G>A strongly influence ischemic stroke risk, their allelic state in haplogroup H1 corroborating its protective effect.
  
  
  CONCLUSIONS
  Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal. arosa@uma.pt
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rosa
authors.forename: Benedita V
authors.initials: BV
authors.lastname: Fonseca
authors.forename: Tiago
authors.initials: T
authors.lastname: Krug
authors.forename: Helena
authors.initials: H
authors.lastname: Manso
authors.forename: Liliana
authors.initials: L
authors.lastname: Gouveia
authors.forename: Isabel
authors.initials: I
authors.lastname: Albergaria
authors.forename: Gisela
authors.initials: G
authors.lastname: Gaspar
authors.forename: Manuel
authors.initials: M
authors.lastname: Correia
authors.forename: Miguel
authors.initials: M
authors.lastname: Viana-Baptista
authors.forename: Rita Moiron
authors.initials: RM
authors.lastname: Simões
authors.forename: Amélia Nogueira
authors.initials: AN
authors.lastname: Pinto
authors.forename: Ricardo
authors.initials: R
authors.lastname: Taipa
authors.forename: Carla
authors.initials: C
authors.lastname: Ferreira
authors.forename: João Ramalho
authors.initials: JR
authors.lastname: Fontes
authors.forename: Mário Rui
authors.initials: MR
authors.lastname: Silva
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Gabriel
authors.forename: Ilda
authors.initials: I
authors.lastname: Matos
authors.forename: Gabriela
authors.initials: G
authors.lastname: Lopes
authors.forename: José M
authors.initials: JM
authors.lastname: Ferro
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Vicente
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Oliveira
mesh_terms: D000328:Adult; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial