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

SUBMITTER: Rosa A

PROVIDER: S-EPMC2492853 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients.

Rosa Alexandra A Fonseca Benedita V BV Krug Tiago T Manso Helena H Gouveia Liliana L Albergaria Isabel I Gaspar Gisela G Correia Manuel M Viana-Baptista Miguel M Simões Rita Moiron RM Pinto Amélia Nogueira AN Taipa Ricardo R Ferreira Carla C Fontes João Ramalho JR Silva Mário Rui MR Gabriel João Paulo JP Matos Ilda I Lopes Gabriela G Ferro José M JM Vicente Astrid M AM Oliveira Sofia A SA

BMC medical genetics 20080701

<h4>Background</h4>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 stro ...[more]

PMID: 18593462

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Project description:Previous studies have suggested that mitochondrial DNA (mtDNA) variants are associated with multiple sclerosis (MS), a complex neurodegenerative immune-mediated disease of the central nervous system. Since mtDNA is maternally inherited without recombination, specific mtDNA variants defining genetic background are associated with the susceptibility to human diseases. To assess the contribution of mtDNA haplogroups to the predisposition of MS in an Arab population, we analysed sequencing data of mitochondrial genomes from 47 native Saudi Arab individuals including 23 patients with relapsing-remitting MS (RRMS) and 24 healthy controls. All patients and controls could be classified into ten haplogroups. The European-specific haplogroup U was more prevalent in patients than in the controls (26.1% vs. 4.2%), whereas haplogroup T was only present in patients and haplogroups HV and N were only found in controls. Haplogroup U was significantly association with increased risk of MS (odds ratio = 6.26, p<0.05), although the association did not maintain significance after adjustment for multiple comparisons. Haplotype U was more prevalent in patients with younger age of onset (p = 0.006), but there was no relationship between haplotype U and disease severity, disease duration or EDSS and age-matched carriers and non-carriers of haplogroup U (p>0.05). Definition site of haplogroup U include the variant m.12308A>G in MT-TL2 gene which was found to affect highly conserved position within the variable arm of tRNALeu(CUN) and thus may impact mitochondrial protein synthesis, and two other variants namely m.11467A>G in MT-ND4 gene and m.12372G>A in MT-ND5 gene which were previously linked with mitochondrial function. Despite the small number of subjects, which may limit the statistical power of the study, our results showed for the first time a possible contribution of haplogroup U to the predisposition to MS in an Arab population. These findings warrant further validation in a large cohort to distinguish a genuine effect specific to MS from a chance finding due to small sampling.

Dataset Information

Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients.

Publications

Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients.

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