Keshan　disease　(KD)　is　an　endemic　dilated　cardiomyopathy　with　unclear　etiology.　In　this　study,　we　compared　mitochondrial-related　gene　expression　profiles　of　peripheral　blood　mononuclear　cells　(PBMCs)　derived　from　16　KD　patients　and　16　normal　controls　in　KD　areas.　Total　RNA　was　isolated,　amplified,　labeled　and　hybridized　to　Agilent　human　4　x　44k　whole　genome　microarrays.　Mitochondrial-related　genes　were　screened　out　by　the　Third-Generation　Human　Mitochondria-Focused　cDNA　Microarray　(hMitChip3).　Quantitative　real-time　PCR,　immunohistochemical　and　biochemical　parameters　related　mitochondrial　metabolism　were　conducted　to　validate　our　microarray　results.　In　KD　samples,　34　up-regulated　genes　(ratios　＞=　2.0)　were　detected　by　significance　analysis　of　microarrays　and　ingenuity　systems　pathway　analysis　(IPA).　The　highest　ranked　molecular　and　cellular　functions　of　the　differentially　regulated　genes　were　closely　related　to　amino　acid　metabolism,　free　radical　scavenging,　carbohydrate　metabolism,　and　energy　production.　Using　IPA,　40　significant　pathways　and　four　significant　networks,　involved　mainly　in　apoptosis,　mitochondrion　dysfunction,　and　nuclear　receptor　signaling　were　identified.　Based　on　our　results,　we　suggest　that　PGC-1　alpha　regulated　energy　metabolism　and　anti-apoptosis　might　play　an　important　role　in　the　compensatory　mechanism　of　MD.　Our　results　may　lead　to　the　identification　of　potential　diagnostic　biomarkers　for　MD　in　PBMCs,　and　may　help　to　understand　the　pathogenesis　of　MD.　(C)　2013　Elsevier　Inc.　All　rights　reserved.