title: Mitochondrial haplogroup background may influence Southeast Asian G11778A Leber hereditary optic neuropathy.
abstract: OBJECTIVE
  To investigate the role of mitochondrial DNA (mt DNA) background on the expression of Leber hereditary optic neuropathy (LHON) in Southeast Asian carriers of the G11778A mutation.
  
  
  METHODS
  Complete mtDNA sequences were analyzed from 53 unrelated Southeast Asian G11778A LHON pedigrees in Thailand and 105 normal Thai controls, and mtDNA haplogroups were determined. Clinical phenotypes were tested for association with mtDNA haplogroup, with adjustment for potential confounders such as sex and age at onset.
  
  
  RESULTS
  mtDNA subhaplogroup B was significantly associated with LHON. Follow-up analysis narrowed the association down to subhaplogroup B5a1 (P = 0.008). Survival analyses with Cox's proportional hazards modeling on 469 samples (91 affected and 378 unaffected), adjusted for sex and heteroplasmy, revealed that haplogroup B5a1 tended to increase the risk of visual loss, but the trend was not statistically significant. Conversely, haplogroup F, the second most common haplogroup in the control population, was the least frequent haplogroup in LHON. This negative association was narrowed down to subhaplogroup F1 (P = 0.00043), suggesting that haplogroup F1 confers a protective effect. The distributions of sex, age at onset and heteroplasmy were not significantly different among haplogroups.
  
  
  CONCLUSIONS
  The specific mtDNA background B5a1 was significantly associated with Southeast Asian G11778A LHON and appeared to modify the risk of visual loss.
authors.affiliation: Department of Biochemistry, Mahidol University, Bangkok, Thailand.
authors.forename: Supannee
authors.initials: S
authors.lastname: Kaewsutthi
authors.forename: Nopasak
authors.initials: N
authors.lastname: Phasukkijwatana
authors.forename: Yutthana
authors.initials: Y
authors.lastname: Joyjinda
authors.forename: Wanicha
authors.initials: W
authors.lastname: Chuenkongkaew
authors.forename: Bussaraporn
authors.initials: B
authors.lastname: Kunhapan
authors.forename: Aung Win
authors.initials: AW
authors.lastname: Tun
authors.forename: Bhoom
authors.initials: B
authors.lastname: Suktitipat
authors.forename: Patcharee
authors.initials: P
authors.lastname: Lertrit
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006238:Haploidy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013785:Thailand / Q000453:epidemiology; D014792:Visual Acuity / Q000235:genetics; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C098483:NADH dehydrogenase subunit 4; D009245:NADH Dehydrogenase