Research article

Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients

Alexandra Rosa¹ , Benedita V Fonseca¹ , Tiago Krug¹ , Helena Manso^1,2 , Liliana Gouveia³ , Isabel Albergaria² , Gisela Gaspar² , Manuel Correia⁴ , Miguel Viana-Baptista⁵ , Rita Moiron Simões⁶ , Amélia Nogueira Pinto⁶ , Ricardo Taipa⁴ , Carla Ferreira⁷ , João Ramalho Fontes⁷ , Mário Rui Silva⁸ , João Paulo Gabriel⁸ , Ilda Matos⁹ , Gabriela Lopes⁴ , José M Ferro³ , Astrid M Vicente^1,2 and Sofia A Oliveira¹

¹Instituto Gulbenkian de Ciência, Oeiras, Portugal

²Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal

³Serviço de Neurologia, Hospital de Santa Maria, Lisboa, Portugal

⁴Serviço de Neurologia, Hospital Geral de Santo António, Porto, Portugal

⁵Serviço de Neurologia, Hospital Garcia de Orta, Almada, Portugal

⁶Serviço de Neurologia, Hospital Fernando Fonseca, Amadora, Portugal

⁷Serviço de Neurologia, Hospital São Marcos, Braga, Portugal

⁸Serviço de Neurologia, Hospital de São Pedro, Vila Real, Portugal

⁹Serviço de Neurologia, Hospital Distrital de Mirandela, Mirandela, Portugal

author email corresponding author email

BMC Medical Genetics 2008, 9:57doi:10.1186/1471-2350-9-57

Published:	1 July 2008

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.

Conclusion

Our data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.