Mitochondrial DNA lineages of African origin confer susceptibility to primary open-angle glaucoma in Saudi patients (original) (raw)
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Molecular vision, 2011
In a previous preliminary analysis we reported that mitochondrial DNA (mtDNA) haplogroup R0a was significantly more frequent in primary angle closure glaucoma (PACG) Saudi patients than in healthy Saudi controls. This result prompted us to extend our work using a significant larger Saudi PACG cohort and more healthy controls. We sequenced the mtDNA regulatory hypervariable region-I (HVS-I) and coding regions, comprising haplogroup diagnostic polymorphisms, in 227 PACG Saudi patients and compared their haplogroup frequencies with those obtained from 186 matched healthy controls (free of PACG by examination) and from a large sample of 810 healthy Saudi Arabs representing the general Saudi population. MtDNA Haplogroups R0a and J, the most abundant lineages in Saudi Arabia, were in significant higher frequencies in the PACG patients than in controls, while the widespread western Eurasian haplogroup U was associated with reduced risk to developing PACG. Haplogroups R0a and J could be anc...
Molecular Vision, 2011
To investigate whether different mitochondrial DNA (mtDNA) haplogroups have a role on the development of pseudoexfoliation glaucoma (PEG) in the Saudi Arab population. Methods: The mtDNA regulatory region and coding regions comprising mtDNA haplogroup diagnostic polymorphisms were sequenced in patients with PEG (n=94), healthy matched controls (free of PEG; n=112) and a healthy Saudi Arab population group (n=810). Results: The Eurasian haplogroup T and the Sub-Saharan African Haplogroup L2 confer susceptibility to PEG, whereas the Eurasian haplogroup N1 was associated with reduced risk to develop PEG in the Saudi Arab population. Conclusions: Mitochondrial haplogroups T and L2 may play a role in the development of PEG in the Saudi Arabian population.
Mitochondrial genetic background in Ghanaian patients with primary open-angle glaucoma
Molecular vision, 2012
Prevalence rates for primary open-angle glaucoma (POAG) are significantly higher in Africans than in European or Asians. It has been reported recently that mitochondrial DNA (mtDNA) lineages of African origin, excluding L2, conferred susceptibility to POAG in Saudi Arabia. This prompted us to test the role of mtDNA haplogroups in the incidence of POAG in the Ghanaian population who has a high frequency of L2 lineages. DNA was extracted from two independent cohorts of clinically diagnosed POAG patients (n=373) and healthy controls (n=451). All patients and controls were from Accra and Tema (the southern region of Ghana). The hypervariable region-I (HVS-I) and coding regions comprising mtDNA haplogroup diagnostic polymorphisms were polymerase chain reaction (PCR) amplified and sequenced in all patients and controls and the haplotypes obtained were assorted into haplogroups and their frequencies compared between cohorts. No statistically significant differences were found in mtDNA hapl...
The role of mitochondrial haplogroups in glaucoma: a study in an Arab population
Molecular vision, 2008
Glaucoma prevalence can vary geographically and ethnically, which suggests that a genetic element could play a significant role. Studies investigating the role of various mitochondrial haplogroups in the pathogenesis of glaucoma are scarce. We compared the prevalence of different mitochondrial haplogroups in 107 glaucoma patients (49 primary open-angle glaucoma, POAG; 29 primary angle-closure glaucoma, PACG; and 29 pseudoexfoliation glaucoma, PEG) and 552 maternally unrelated normal controls. All patients and controls were Saudi Arabs. There was no statistically significant difference between patients and controls for all mitochondrial haplogroups tested except for PACG patients with mitochondrial haplogroup preHV1 (odds ratio=4.9; 95% CI 2.3 - 10.5; p=0.00002). Patients with preHV1 mitochondrial haplogroups are at higher risk of developing PACG. However, our study group is relatively small and further studies with more patients in other populations are needed to confirm this intere...
The Role of Mitochondrial Haplogroups in Glaucoma: A Study in the Saudi Population
2009
Purpose: Glaucoma prevalence can vary geographically and ethnically, which suggests that a genetic element could play a significant role. Studies investigating the role of various mitochondrial haplogroups in the pathogenesis of glaucoma are scarce. Methods: We compared the prevalence of different mitochondrial haplogroups in 107 glaucoma patients (49 primary open-angle glaucoma, POAG; 29 primary angle-closure glaucoma, PACG; and 29 pseudoexfoliation glaucoma, PEG) and 552 maternally unrelated normal controls. All patients and controls were Saudi Arabs. Results: There was no statistically significant difference between patients and controls for all mitochondrial haplogroups tested except for PACG patients with mitochondrial haplogroup preHV1 (odds ratio=4.9; 95% CI 2.3 -10.5; p=0.00002). Conclusions: Patients with preHV1 mitochondrial haplogroups are at higher risk of developing PACG. However, our study group is relatively small and further studies with more patients in other populations are needed to confirm this interesting finding.
Mitochondrial DNA Variation and Disease Susceptibility in Primary Open-Angle Glaucoma
Investigative ophthalmology & visual science, 2018
To determine whether mitochondrial DNA haplogroups or rare variants associate with primary open-angle glaucoma in subjects of European descent. A case-control comparison of age- and sex-matched cohorts of 90 primary open-angle glaucoma patients and 95 population controls. Full mitochondrial DNA sequences from peripheral blood were generated by next-generation sequencing and compared to the revised Cambridge Reference Sequence to define mitochondrial haplogroups and variants. Most subjects were of the major European haplogroups H, J, K, U, and T. Logistic regression analysis showed haplogroup U to be significantly underrepresented in male primary open-angle glaucoma subjects (odds ratio 0.25; 95% confidence interval [CI] 0.09-0.67; P = 0.007; Bonferroni multiple testing P = 0.022). Variants in the mitochondrial DNA gene MT-ND2 were overrepresented in the control group (P = 0.005; Bonferroni multiple testing correction P = 0.015). Mitochondrial DNA ancestral lineages modulate the risk...
Mitochondrial DNA nucleotide changes in primary congenital glaucoma patients
Molecular vision, 2013
Primary congenital glaucoma (PCG) is the second most common cause of blindness, accounting for 0.01%-0.04% of total blindness worldwide. Most congenital glaucoma cases are mapped to the GLC3A locus, and many aspects of PCG are still unknown. Recent studies have reported an increased frequency of mitochondrial DNA (mtDNA) sequence changes in primary open-angle glaucoma, primary angle-closure glaucoma, and pseudoexfoliation glaucoma compared to controls. Thus, this study was planned with the aim of detecting mitochondrial DNA variations in PCG cases. Twenty primary congenital glaucoma cases were selected from Dr. R. P. Centre for Ophthalmic Sciences of All India Institute of Medical Sciences (AIIMS), New Delhi, India. DNA was isolated from whole blood samples. The entire coding region of the mitochondrial genome was amplified by PCR in 20 patients and 20 controls. The full mtDNA genome was sequenced and analyzed against mitochondrial reference sequence NC_012920. MtDNA sequencing reve...
Investigative ophthalmology & visual science, 2016
Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure. We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated wit...
Investigative Ophthalmology & Visual Science, 2013
Word Count: 245 Main Text Word Count: 2,555 Abstract Purpose Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. Methods We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22
Mitochondrial DNA analysis in primary congenital glaucoma
Molecular vision, 2010
To screen mitochondrial DNA (mtDNA) for nucleotide variations in primary congenital glaucoma (PCG). The entire coding region of the mitochondrial genome was amplified by polymerase chain reaction from 35 PCG patients and 40 controls. The full mtDNA genome except the D-loop was sequenced. All sequences were analyzed against mitochondrial reference sequence NC_012920. MtDNA sequencing revealed a total of 132 and 58 nucleotide variations in PCG and controls, respectively. Of 132 nucleotide variations, 42 (31.81%) were non-synonymous and 82 (62.12%) were synonymous changes, and 8 were in RNA genes. The highest number of nucleotide variations were recorded in complex I followed by complex IV, then complex V. Eight patients (22.85%) had potentially pathogenic mtDNA nucleotide changes and twenty (57.14%) had mtDNA sequence changes associated with elevated reactive oxygen species (ROS) production. Mitochondria not only constitute the energy-generating system in the cell, but are also critic...