Mitochondrial Haplogroups and Control Region Polymorphisms in Age-Related Macular Degeneration: A Case-Control Study

Background: Onset and development of the multifactorial disease age-related macular degeneration (AMD) are highly interrelated with mitochondrial functions such as energy production and free radical turnover. Mitochondrial dysfunction and overproduction of reactive oxygen species may contribute to destruction of the retinal pigment epithelium, retinal atrophy and choroidal neovascularization, leading to AMD. Consequently, polymorphisms of the mitochondrial genome (mtDNA) are postulated to be susceptibility factors for this disease. Previous studies from Australia and the United States detected associations of mitochondrial haplogroups with AMD. The aim of the present study was to test these associations in Middle European Caucasians. Methodology/Principal Findings: Mitochondrial haplogroups (combinations of mtDNA polymorphisms) and mitochondrial CR polymorphisms were analyzed in 200 patients with wet AMD (choroidal neovascularization, CNV), in 66 patients with dry AMD, and in 385 controls from Austria by means of multiplex primer extension analysis and sequencing, respectively. In patients with CNV, haplogroup H was found to be significantly less frequent compared to controls, and haplogroup J showed a trend toward a higher frequency compared to controls. Five CR polymorphisms were found to differ significantly in the two study populations compared to controls, and all, except one (T152C), are linked to those haplogroups. Conclusions/Significance: It can be concluded that haplogroup J is a risk factor for AMD, whereas haplogroup H seems t

Straylight Effects with Aging and Lens Extraction

Purpose: To assess possible gains and losses in straylight values among the population to consider straylight as added benefit of lens extraction. Design: In this cross-sectional design, data from a multicenter study on visual function in automobile drivers were analyzed. Methods: On both eyes of 2,422 subjects, visual acuity (logarithm of the minimum angle of resolution [logMAR] in steps of 0.02 log units), straylight on the retina (psychophysical compensation comparison method), and lens opacity (slit-lamp scoring using the Lens Opacities Classification System III [LOCS III] system) were determined. Three groups were defined: 220 pseudophakic eyes, 3,182 noncataractous eyes (average LOCS III score, 3.0). Results: Noncataractous straylight values increases strongly with age as: log(s) = constant + log(1 + (age / 65)4), doubling by the age of 65 years, and tripling by the age of 77 years. Population standard deviation around this age norm was approximately 0.10 log units. The cataract eyes (in this active driver group) had relatively mild straylight increase. In pseudophakia, straylight values may be very good, better even than in the noncataract group. Visual acuity and straylight were found to vary quite independently. Conclusions: Lens extraction holds promise not only to improve on the condition of the cataract eye, but also to improve on the age-normal eye. Lens extraction potentially reverses the strong age increase in straylight value, quite independently from visual acuity

Frequencies (%) of control region polymorphisms >5% in patients with CNV and in controls as well as the corresponding odds ratios and 95% confidence intervals.

a<p>mtDNA = mitochondrial DNA.</p>b<p>CNV = choroidal neovascularisation.</p>c<p>n: number of individuals with the respective polymorphism.</p>d<p>P-value: Pearson chi-square or Fisher's exact test.</p>e<p>CI = confidence interval.</p>f<p>adjusted for age and sex by logistic regression analysis.</p

Comparison of age-related macular degeneration case-control studies in the literature with the present study.

a<p>mtDNA = mitochondrial DNA.</p>b<p>According to PhyloTree.org <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030874#pone.0030874-vanOven1" target="_blank">[21]</a>.</p>c<p>P-values: present study: adjusted for age and sex. Jones et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030874#pone.0030874-Jones1" target="_blank">[12]</a>: adjusted for age, sex and current smoking. Canter et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030874#pone.0030874-Canter1" target="_blank">[13]</a>: adjusted for sex and three nuclear polymorphisms (CFH-Complement Factor H gene, rs1061170; LOC387715, rs10490924; APOE, ApoE2 allele). Udar et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030874#pone.0030874-Udar1" target="_blank">[14]</a>: no adjustment. SanGiovanni et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030874#pone.0030874-SanGiovanni1" target="_blank">[15]</a>: adjusted for age, sex and smoking.</p>d<p>CI = confidence interval.</p

Characteristics of the study populations.

a<p>CNV = choroidal neovascularization.</p>b<p>AMD = age-related macular degeneration.</p>c<p>SD = standard deviation.</p

Frequencies (%) of mitochondrial haplogroups in Caucasian patients with CNV and in controls.

a<p>CNV = choroidal neovascularization.</p>b<p>P-value: Pearson chi-square or Fisher's exact test.</p>c<p>Haplogroups that could not be assigned to one of the nine major European haplogroups by the SNP combination.</p