Mitochondrial DNA Haplogroup Distribution in Pedigrees of Southeast Asian G11778A Leber Hereditary Optic Neuropathy

Tharaphan, Pattamon; Chuenkongkaew, Wanicha; Luangtrakool, Komon; Sanpachudayan, Thitima; Suktitipat, Bhoom; Suphavilai, Rungnapa; Srisawat, Chatchawan; Sura, Thanyachai; Lertrit, Patcharee

doi:10.1097/01.wno.0000249318.88991.c4

Cited by 19 publications

(13 citation statements)

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“…Other N and R macro-groups made up the remaining 20%. These frequencies are similar to those seen in HIV-negative Thai populations [35–37]. Since DNA was available for all study participants, including those without ENFD, we were able to confirm that distribution of major mtDNA haplogroups did not differ significantly between those with and without ENFD data (data not shown).…”

Section: Resultssupporting

confidence: 79%

“…Similar studies from HIV-infected persons of European ancestry have reported such differences [40,41]. Although population-based data from Thailand are limited, mtDNA haplogroup frequencies have been similar to those previously reported [35–37], arguing against a significant impact of haplogroup on HIV acquisition risk. Nonetheless, the similar ENFD at baseline and ENFD gain on ART among the B haplogroup despite being older (and independent of other risk factors for ENFD change in this population) are notable and merit further study.…”

Section: Discussionsupporting

confidence: 82%

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Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy

Hulgan

Levinson

Gerschenson

et al. 2014

Aids

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Objective We explored associations between mitochondrial DNA (mtDNA) haplogroups, epidermal nerve fiber density (ENFD), and HIV-associated sensory neuropathy (HIV-SN) in a randomized trial of Thai patients initiating antiretroviral therapy (ART). Design The South East Asia Research Collaboration with Hawaii 003 study evaluated toxicity of nucleoside reverse transcriptase inhibitors (stavudine vs. zidovudine vs. tenofovir). We present secondary analyses of mtDNA haplogroups and ENFD changes. Methods ENFD, peripheral blood mononuclear cell mitochondrial complex I and IV, and 8-oxo-deoxyguanine (8-oxo-dG) were quantified. Peripheral blood mononuclear cell mtDNA sequences were obtained for haplogroup determination. Multivariate regression of ENFD change was performed. Results Paired ENFD was available from 118 patients. Median age, CD4+ cell count, and height at entry were 34 years, 172 cells/μl, and 162 cm, respectively. Major haplogroups included M (42%), F (21%), and B (16%). Baseline ENFD, CD4+ cell count, randomized ART, and biomarkers did not differ by haplogroup. Haplogroup B patients were older (P=0.02) at baseline, and had an increase in median ENFD (+1.5 vs. −2.9 fibers/mm; P=0.03) and 8-oxo-dG break frequency (+0.05 vs. 0.00; P=0.05) compared to other haplogroups. In a multivariate model, haplogroup B was associated with increased ENFD (β=3.5, P=0.009) at week 24, whereas older age (P=0.02), higher baseline CD4+ cell count, (P=0.03), higher complex I level (P=0.03), and higher ENFD (P<0.001) at baseline were all associated with decreased ENFD. Three of the six HIV-SN cases were haplogroup B (P=0.05). Conclusions Thai persons belonging to mtDNA haplogroup B had increased ENFD and 8-oxo-dG on ART, and were more likely to develop HIV-SN. These results suggest that mtDNA variation influences early oxidative damage and ENFD changes.

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Section: Resultssupporting

confidence: 79%

Section: Discussionsupporting

confidence: 82%

Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy

Hulgan

Levinson

Gerschenson

et al. 2014

Aids

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“…In the pooled Han Chinese from general populations, this haplogroup had a frequency of 16.7% (68/408), much higher than what we observed for the LHON subjects with m.14484T>C (1.9%; 1/52). This result was unexpected, but a extremely low occurrence of haplogroup F had been observed in Chinese LHON patients with m.11778G>A (2.2%; 4/182) [15] and in 40 LHON patients harboring m.11778G>A from Thailand (0%; 0/40) [38]. The exact reason for the low occurrence of haplogroup F in Chinese LHON families with m.14484T>C and m.11778G>A remains unclear.…”

Section: Discussionmentioning

confidence: 89%

Mitochondrial DNA Sequence Variation and Haplogroup Distribution in Chinese Patients with LHON and m.14484T>C

Jia

Zhang

et al. 2010

PLoS ONE

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BackgroundLeber hereditary optic neuropathy (LHON, MIM 535000) is one of the most common mitochondrial genetic disorders caused by three primary mtDNA mutations (m.3460G>A, m.11778G>A and m. 14484T>C). The clinical expression of LHON is affected by many additional factors, e.g. mtDNA background, nuclear genes, and environmental factors. Hitherto, there is no comprehensive study of Chinese LHON patients with m.14484T>C.Methodology/Principal FindingsIn this study, we analyzed the mtDNA sequence variations and haplogroup distribution pattern of the largest number of Chinese LHON patients with m.14484T>C to date. We first determined the complete mtDNA sequences in eleven LHON probands with m.14484T>C, to discern the potentially pathogenic mutations that co-segregate with m.14484T>C. We then dissected the matrilineal structure of 52 patients with m.14484T>C (including 14 from unrelated families and 38 sporadic cases) and compared it with the reported Han Chinese from general populations. Complete mtDNA sequencing showed that the eleven matrilines belonged to nine haplogroups including Y2, C4a, M8a, M10a1a, G1a1, G2a1, G2b2, D5a2a1, and D5c. We did not identify putatively pathogenic mutation that was co-segregated with m.14484T>C in these lineages based on the evolutionary analysis. Compared with the reported Han Chinese from general populations, the LHON patients with m.14484T>C had significantly higher frequency of haplogroups C, G, M10, and Y, but a lower frequency of haplogroup F. Intriguingly, we also observed a lower prevalence of F lineages in LHON subjects with m.11778G>A in our previous study, suggesting that this haplogroup may enact similar role during the onset of LHON in the presence of m.14484T>C or m.11778G>A.Conclusions/SignificanceOur current study provided a comprehensive profile regarding the mtDNA variation and background of Chinese patients with LHON and m.14484T>C. Matrilineal background might affect the expression of LHON in Chinese patients with m.14484T>C.

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“…Three of these families contained several people with the heteroplasmic mutation (F09, F24, F28), while the other family was homoplasmic (F30). All pedigrees belong to macrohaplogroup M (Tharaphan et al 2006).…”

Section: Resultsmentioning

confidence: 99%

Transmission of heteroplasmic G11778A in extensive pedigrees of Thai Leber hereditary optic neuropathy

et al. 2006

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Mitochondrial DNA Haplogroup Distribution in Pedigrees of Southeast Asian G11778A Leber Hereditary Optic Neuropathy

Cited by 19 publications

References 19 publications

Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy

Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy

Mitochondrial DNA Sequence Variation and Haplogroup Distribution in Chinese Patients with LHON and m.14484T>C

Transmission of heteroplasmic G11778A in extensive pedigrees of Thai Leber hereditary optic neuropathy

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