Mitochondrial haplogroup H1 is protective for ischemic stroke in Portuguese patients

Abstract

BackgroundThe 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.MethodsWe 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.ResultsHaplogroup 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.ConclusionOur data suggests that mitochondrial haplogroup H1 has an impact on ischemic stroke risk in a Portuguese sample.

Mitochondrial haplogroup D4 confers resistance and haplogroup B is a genetic risk factor for high-altitude pulmonary edema among Han Chinese

“…This substitution has arisen independently in several mtDNA haplogroups, including J1, D4, and H1. Interestingly, 3010A has been proposed to contribute to the protective effects of haplogroup H1 against ischemic stroke (Rosa et al, 2008). This mtSNP is also enriched in Japanese centenarians (Alexe et al, 2007), and subgroup D4a is a marker for extreme longevity (Bilal et al, 2008).…”

Comparison of telomere length between population-specific mitochondrial haplogroups among different age groups in a Latvian population

“…In particular, different hgs were associated with Leber's hereditary optic neuropathy, ichemic stroke, coronary artery disease and diabetic retinopathy and osteoarthritis (OA) (Torroni et al, 1997;Hudson et al, 2007;Kofler et al, 2009;Rego-Pérez et al, 2008). Other studies have found an effect of some hgs against ischemic stroke, Alzheimer disease and Parkinson's disease van der Walt et al, 2003;Ghezzi et al, 2005;Gaweda-Walerych et al, 2008;Rosa et al, 2008).…”

Association of a Genetic Variant in the <i>ALOX5AP</i> with Higher Risk of Ischemic Stroke: A Case-Control, Meta-Analysis and Functional Study

“…Portuguese IS cases were unrelated patients, who were under the age of 65 at stroke onset and were recruited throughout Portugal. Stroke was defined by the presence of a new focal neurological deficit, with an acute onset and symptoms and signs persisting for more than 24 h, and confirmed by computed tomography scan and/or magnetic resonance imaging [26]. Control participants were healthy volunteers free of stroke as ascertained by direct interview before recruitment.…”