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

BMC Medical Genetics

Nitin Udar⁵  David S Boyer²  Anthony B Nesburn¹  Kent Small¹  Jonathan Langberg⁵  Jacqueline King⁵  Masood Memarzadeh⁵  Feilin Zhu⁵  Marilyn Chwa⁵  Elizabeth Yang³  Andrew Nobe⁵  Kyaw Soe⁵  Nikan Khatibi⁵  Shari R Atilano⁵  Garrick Chak⁵  Dieter Hertzog⁴  M Cristina Kenney⁵ 

[1] Cedars-Sinai Medical Center, Los Angeles, CA, USA;Retina-Vitreous Associates Medical Group, Beverly Hills, CA, USA;Northwestern Feinberg School of Medicine, Chicago, IL, USA;Loma Linda University School of Medicine, Loma Linda, CA, USA;Gavin Herbert Eye Institute, Univeresity of California Irvine, Hewitt Hall, Room 2028, 843 Health Science Rd, Irvine, CA 92697, USA

关键词: ARMS2;    CFH;    mtDNA;    Mitochondrial haplogroups;    Age-related macular degeneration;   

Others  :  1177751
DOI  :  10.1186/1471-2350-14-4

 received in 2012-05-21, accepted in 2012-12-17,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Kenney et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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