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Reinhard Told, Doreen Schmidl, Agnes Boltz, Stefan Palkovits, Semira Kaya, Gerhard Garhofer, Leopold Schmetterer; Complement Factor H Gene Polymorphism Plays A Role In The Regulation Of Vascular Tone In The Choroid. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4157.
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We have previously shown that choroidal blood flow in healthy subjects shows some degree of regulation during isometric exercise. In the recent years there is increasing evidence that polymorphisms in the complement factor H gene are significantly associated with age-related macular degeneration. Interestingly, complement factor H deficient mice show abnormal ocular vasculature characterized by severe endothelial damage. In the present study we hypothesized that the carriers of CC at rs1061170, which have an increased risk of AMD, already show abnormal choroidal blood flow regulation at ages below 35 years.
A total of 99 healthy subjects (aged between 19 and 35 years) were included in this study. The effect of 6 minutes of isometric exercise on choroidal blood flow was investigated and genotyping at rs1061170 was performed. Ocular perfusion pressure (OPP) was calculated as 2/3*mean arterial pressure-intraocular pressure. ChBF was measured using laser Doppler flowmetry.
Out of the 99 subjects 18 were homocygous for the CC allele, 50 were homocygous for the TT allele and 31 subjects were heterocygous. In 3 carriers no adequate laser Doppler signal could be obtained, so the data arise from the remaining 96 subjects. The response in OPP was similar between the three studied groups (p=0.263). By contrast, the increase in ChBF was more pronounced in the carriers of the CC allele, than in the carriers of the TT allele or the heterozygous subjects (p = 0.043). This difference is also visible when looking into the pressure/flow relationship during isometric exercise. ChBF started to increase at an OPP increase of 64.9% and 66.5% in carriers of the TT allele and heterocygous subjects, respectively. In subjects subjects homocygous for the CC allele this increase was seen already earlier (OPP increase of 46.7% above baseline).
Our data indicate that healthy young carriers of the CC allele at rs1061170 show abnormal choroidal blood flow regulation. This is interesting, because elderly subjects with this genotype are at increased risk of having AMD. Previously complement factor H polymorphisms were primarily linked to AMD via inflammatory processes. The present study indicates that they may also be linked to hypoxia and further studies are warranted to support this assumption.
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