SHORT COMMUNICATION No evidence of association between frontotemporal dementia and major European mtDNA haplogroups G. Rose a , T. Longo a , R. Maletta b , G. Passarino a , A. C. Bruni b and G. De Benedictis a a Department of Cell Biology, University of Calabria, Rende, Italy; and b Regional Neurogenetic Centre, ASL 6, Lamezia Terme, CZ, Italy Keywords: frontotemporal dementia, mtDNA, risk factors Received 2 April 2008 Accepted 23 May 2008 Background and purpose: Mitochondrial DNA (mtDNA) inherited variability (hap- logroup/sub-haplogroup) is currently emerging as not being neutral with respect to several complex traits like neurodegenerative diseases. Here we investigated the as- sociation of European mtDNA haplogroups/sub-haplogroups with frontotemporal dementia (FTD). Method and Results: A case-control study was carried out on 114 patients with FTD (68 sporadic and 46 familial) and 180 controls, matched for age, gender and ethnicity. No association was found. Conclusions: European mtDNA haplogroups/sub-haplogroups are unlikely to play a major role in the risk of devel- oping the disease. Introduction Frontotemporal dementia (FTD) is a complex and heterogeneous disease, more common than previously thought, whose aetiology still remains elusive. Although causative mutations have rarely been found in a few genes (such as MAPT and PRGN, accounting for up to 2.9 and 4.8% of the cases) [1], FTD usually appears as a complex trait where susceptibility is due to the common variability in a number of genes [2]. mtDNA variability may affect susceptibility to neurodegenerative diseases, because of the essential role played by mitochondria in energy metabolism and apoptosis. In fact, mitochondria are essential for neuronal function because neurons are highly dependent on oxidative phosphorylation for their energetic needs, and oxidative damage is observed in all classes of organic molecules (proteins, lipids, nucleic acids and sugars) that are critical for structural and functional neuronal integrity [3]. mtDNA variation has been well characterized at the population level. Based on the information obtained from RFLP analysis and from sequence analysis of the hypervariable segments HVS-I and HVS-II (control region), several haplogroups (clusters of ancient shared variants) have been described [4,5]. Whether mtDNA-inherited variability does contribute to FTD has not been investigated till now. Aim of this work was to test the hypothesis that the major European mtDNA haplogroups play a role in the onset of FTD. Materials and methods Sample A sample of 114 unrelated patients with FTD was recruited at the Regional Neurogenetics Centre (Calabria, southern Italy). Patients without other af- fected members in the family were classified as affected by sporadic FTD (n = 68 subjects). On the contrary, patients with a positive family history of FTD were classified as affected by familial FTD (n = 46 subjects). Diagnosis of FTD was assessed by using multiple operational criteria and was based on specific clinical- neuropsychological features and neuroradiological profiles (for details see ref. [2] and references therein). A control group of 180 unrelated subjects matched for age, sex and ethnicity was recruited in the same popu- lation. The same complete set of clinical-laboratory procedures and neurological assessment of cognitive status used for patients were also performed in the control group. In addition, a previous screening carried out by using sequence analysis on MAPT gene failed to find any mutations in this sample [2]. The age range in each of the three sample groups was as follows: 40–80 years in the sporadic FTD group (median age 68.0 years, 30 men and 38 women); 45–80 years in the familial FTD group (median age 54.5 years; 23 men and 23 women) and 40–80 years in the control group (median age 66.5 years, 84 men and 96 women). The study was approved by the Ethical Committee of the University of Calabria and informed consent for research purposes was obtained from all individuals involved in the study; for disabled patients with FTD consent was given by their legal tutors. Correspondence: Prof. Giuseppina Rose, Department of Cell Biology, University of Calabria, 87036 Rende, Italy (tel.: +39 984 492931; fax: +39 984 492911; e-mail: pinarose@unical.it). 1006 Ó 2008 The Author(s) Journal compilation Ó 2008 EFNS European Journal of Neurology 2008, 15: 1006–1008 doi:10.1111/j.1468-1331.2008.02222.x