Evidence for Sub-Haplogroup H5 of Mitochondrial DNA as a Risk Factor for Late Onset Alzheimer's Disease

BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p=0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p=0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. CONCLUSIONS: Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups and the accumulation of sporadic mutations associated with complex traits such as AD

Efficacy of educational intervention to improve awareness of the importance of iodine, use of iodized salt, and dietary iodine intake in northeastern Italian schoolchildren

OBJECTIVE: An educational program was conducted among school-aged children to improve their knowledge about iodine prophylaxis, their iodine status, and their dietary habits. METHODS: At the baseline (T0) and after 6\u2009mo (T1), participants (970 at T0 and 949 at T1) answered questionnaires testing their knowledge about iodine prophylaxis and their eating habits. Urine samples were collected from a randomly selected subgroup of participants (313 at T0 and 312 at T1). RESULTS: From T0 to T1 there was a significant improvement in respondents' knowledge about iodine prophylaxis (from 44% to 70%), iodized salt consumption (from 78% to 84%), and median urine iodine concentrations (from 70\u2009\ub5g/L to 91\u2009\ub5g/L). Milk and iodized salt intakes were associated with a better iodine status per se, and more so when used simultaneously. Girls drank milk less often than boys did (daily in 52% and 59% of cases, respectively). Children of foreign origin ate sodium-rich food more often than Italians did. CONCLUSION: Educational intervention improved the children's knowledge about iodine prophylaxis and use of iodized salt. Consuming salt in addition to milk improves iodine status. Children of foreign origin have different eating habits