RESUMO
MtDNA haplogroups J and K have been associated with a decreased risk of developing Parkinson's disease (PD). To confirm this finding, we compared the distribution of mtDNA haplogroups J and K in a large sample of Australian patients with PD (n = 890) to population-based controls (n = 3,491). We assigned subjects to haplogroups J or K using standard PCR/RFLP techniques. Of the 890 subjects with PD, 10.6% were haplogroup J (95% CI 8.6-12.8, n = 94) and 7.1% were haplogroup K (95% CI 5.5-8.9, n = 63). In our controls, 10.2% belonged to haplogroup J (95% CI 9.2-11.2, n = 356), and 7.8% were in haplogroup K (95% CI 6.9-8.7, n = 272). There was no significant difference in the prevalence of mtDNA haplogroup J or K in PD patients compared to population-based controls. Our findings indicate that mtDNA haplogroups J and K are not associated with a lower risk of PD.
Assuntos
DNA Mitocondrial/genética , Haplótipos/genética , Doença de Parkinson/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Estudos de Casos e Controles , DNA Mitocondrial/classificação , Europa (Continente)/etnologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Doença de Parkinson/etnologia , Polimorfismo de Nucleotídeo Único , Risco , População Branca/genéticaRESUMO
OBJECTIVE: To determine whether variants of the mitochondrial genome influence the risk of developing age-related hearing loss (ARHL). DESIGN: Cross-sectional study. SETTING: Eligible participants were noninstitutionalized permanent residents 49 years or older identified in a door-to-door census of 2 suburban postcode areas, west of Sydney, Australia. PARTICIPANTS: The Blue Mountains Hearing Study (BMHS) was a population-based survey of hearing loss, conducted during 1997 to 1999, among the participants of the Blue Mountains Eye Study cohort. MAIN OUTCOME MEASURES: We defined hearing impairment as the pure-tone average of audiometric hearing thresholds at 500, 1000, 2000, and 4000 Hz (> 25- but 40- but 60-dB HL [severe hearing loss]) in the better of the 2 ears. RESULTS: Of the 2765 BMHS participants, 912 (33%) were found to have ARHL. After adjusting for other hearing loss risk factors, mitochondrial DNA (mtDNA) haplogroups U and K were independently associated with a higher prevalence of ARHL compared with subjects with other haplogroups. Haplogroup U was significantly associated with moderate to severe ARHL (multivariable-adjusted odds ratio, 1.63; 95% confidence interval, 1.10-2.41). Haplogroup K was associated with severity types of ARHL in persons aged 50 to 59 years (odds ratio, 3.02; 95% confidence interval, 1.30-6.99). There was also a joint effect between mtDNA haplogroups U and K and other known hearing loss risk factors such as diabetes and past noise exposure. CONCLUSION: Findings from this older Australian population demonstrate an association between certain mtDNA haplogroups and ARHL, as well as a link to the susceptibility of other known risk factors for ARHL.
Assuntos
DNA Mitocondrial/genética , Haplótipos/genética , Presbiacusia/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Frequência do Gene/genética , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , New South Wales , Presbiacusia/epidemiologiaRESUMO
OBJECTIVE: To investigate whether mitochondrial haplogroups are associated with age-related maculopathy (ARM). METHODS: We assessed the association between mitochondrial haplogroups and ARM in a population-based sample of 3509 persons aged 49 years or older residing west of Sydney. Retinal photographs of both eyes were taken (1999-2001) and subsequently graded for ARM following the Wisconsin grading system. Genetic analysis for mitochondrial DNA haplogroups was performed. Associations between these genetic markers and risk factors for ARM were assessed. RESULTS: After adjusting for age, sex, and smoking, haplogroup H was associated with a reduced prevalence of any (early and late) ARM (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.58-0.97), early ARM (OR, 0.75; 95% CI, 0.57-0.98), and large distinct and indistinct soft drusen (OR, 0.70; 95% CI, 0.56-0.89). Haplogroup J was associated with a higher prevalence of large, soft distinct drusen (OR, 1.80; 95% CI, 1.18-2.73). Haplogroup U was associated with an increased prevalence of retinal pigment abnormalities (OR, 1.45; 95% CI, 1.11-1.91). CONCLUSIONS: Our findings of associations between different haplogroup types and prevalent ARM or ARM lesions suggest that these haplogroups may be genetic markers indicative of an individual's susceptibility to ARM.
Assuntos
DNA Mitocondrial/genética , Haplótipos , Degeneração Macular/genética , Mitocôndrias/genética , Idoso , Idoso de 80 Anos ou mais , Fator H do Complemento/genética , Feminino , Frequência do Gene , Marcadores Genéticos , Humanos , Degeneração Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , New South Wales , Prevalência , Fatores de RiscoRESUMO
We aimed to establish the population prevalence of the MELAS 3243A>G mtDNA mutation in a large Caucasian-based population (n=2954; 99% Caucasian, 57% women and mean age of 66.4 years). All participants underwent comprehensive clinical evaluation including audiologic testing. We detected the 3243A>G mutation in seven subjects using standard polymerase chain reaction/restriction fragment length polymorphism methods, establishing a population prevalence of 236/100000 (0.24%; 95% CI 0.10-0.49%); much higher than previously reported. All had mild to moderate hearing loss. Our findings indicate that subjects with the 3243A>G mtDNA mutation could be markedly under-recognised in the community.
