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Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the asso...

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Autores principales: Kenney, M Cristina, Hertzog, Dieter, Chak, Garrick, Atilano, Shari R, Khatibi, Nikan, Soe, Kyaw, Nobe, Andrew, Yang, Elizabeth, Chwa, Marilyn, Zhu, Feilin, Memarzadeh, Masood, King, Jacqueline, Langberg, Jonathan, Small, Kent, Nesburn, Anthony B, Boyer, David S, Udar, Nitin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566905/
https://www.ncbi.nlm.nih.gov/pubmed/23302509
http://dx.doi.org/10.1186/1471-2350-14-4
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author Kenney, M Cristina
Hertzog, Dieter
Chak, Garrick
Atilano, Shari R
Khatibi, Nikan
Soe, Kyaw
Nobe, Andrew
Yang, Elizabeth
Chwa, Marilyn
Zhu, Feilin
Memarzadeh, Masood
King, Jacqueline
Langberg, Jonathan
Small, Kent
Nesburn, Anthony B
Boyer, David S
Udar, Nitin
author_facet Kenney, M Cristina
Hertzog, Dieter
Chak, Garrick
Atilano, Shari R
Khatibi, Nikan
Soe, Kyaw
Nobe, Andrew
Yang, Elizabeth
Chwa, Marilyn
Zhu, Feilin
Memarzadeh, Masood
King, Jacqueline
Langberg, Jonathan
Small, Kent
Nesburn, Anthony B
Boyer, David S
Udar, Nitin
author_sort Kenney, M Cristina
collection PubMed
description BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924) and CFH (T > C; Try402His, rs1061170). METHODS: Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene. RESULTS: The JTU haplogroup cluster occurred in 34% (55/162) of AMD subjects versus 15% (24/164) of normal (OR = 2.99; p = 0.0001). This association was slightly greater in males (OR = 3.98, p = 0.005) than the female population (OR = 3.02, p = 0.001). Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001) and CFH (rs1061170; p = 0.027) SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924) or CFH (rs1061170) SNPs on the JTU haplogroup background. CONCLUSIONS: There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924) and CFH (rs1061170) genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD.
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spelling pubmed-35669052013-02-11 Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study Kenney, M Cristina Hertzog, Dieter Chak, Garrick Atilano, Shari R Khatibi, Nikan Soe, Kyaw Nobe, Andrew Yang, Elizabeth Chwa, Marilyn Zhu, Feilin Memarzadeh, Masood King, Jacqueline Langberg, Jonathan Small, Kent Nesburn, Anthony B Boyer, David S Udar, Nitin BMC Med Genet Research Article BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in elderly, Caucasian populations. There is strong evidence that mitochondrial dysfunction and oxidative stress play a role in the cell death found in AMD retinas. The purpose of this study was to examine the association of the Caucasian mitochondrial JTU haplogroup cluster with AMD. We also assessed for gender bias and additive risk with known high risk nuclear gene SNPs, ARMS2/LOC387715 (G > T; Ala69Ser, rs10490924) and CFH (T > C; Try402His, rs1061170). METHODS: Total DNA was isolated from 162 AMD subjects and 164 age-matched control subjects located in Los Angeles, California, USA. Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the J, U, T, and H mitochondrial haplogroups and the ARMS2-rs10490924 and CFH-rs1061170 SNPs. PCR amplified products were sequenced to verify the nucleotide substitutions for the haplogroups and ARMS2 gene. RESULTS: The JTU haplogroup cluster occurred in 34% (55/162) of AMD subjects versus 15% (24/164) of normal (OR = 2.99; p = 0.0001). This association was slightly greater in males (OR = 3.98, p = 0.005) than the female population (OR = 3.02, p = 0.001). Assuming a dominant effect, the risk alleles for the ARMS2 (rs10490924; p = 0.00001) and CFH (rs1061170; p = 0.027) SNPs were significantly associated with total AMD populations. We found there was no additive risk for the ARMS2 (rs10490924) or CFH (rs1061170) SNPs on the JTU haplogroup background. CONCLUSIONS: There is a strong association of the JTU haplogroup cluster with AMD. In our Southern California population, the ARMS2 (rs10490924) and CFH (rs1061170) genes were significantly but independently associated with AMD. SNPs defining the JTU mitochondrial haplogroup cluster may change the retinal bioenergetics and play a significant role in the pathogenesis of AMD. BioMed Central 2013-01-09 /pmc/articles/PMC3566905/ /pubmed/23302509 http://dx.doi.org/10.1186/1471-2350-14-4 Text en Copyright ©2013 Kenney et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kenney, M Cristina
Hertzog, Dieter
Chak, Garrick
Atilano, Shari R
Khatibi, Nikan
Soe, Kyaw
Nobe, Andrew
Yang, Elizabeth
Chwa, Marilyn
Zhu, Feilin
Memarzadeh, Masood
King, Jacqueline
Langberg, Jonathan
Small, Kent
Nesburn, Anthony B
Boyer, David S
Udar, Nitin
Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
title Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
title_full Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
title_fullStr Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
title_full_unstemmed Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
title_short Mitochondrial DNA haplogroups confer differences in risk for age-related macular degeneration: a case control study
title_sort mitochondrial dna haplogroups confer differences in risk for age-related macular degeneration: a case control study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566905/
https://www.ncbi.nlm.nih.gov/pubmed/23302509
http://dx.doi.org/10.1186/1471-2350-14-4
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