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P.A. Radenbaugh, N.C. McLaren, A. Goyal, D.M. Reed, C.A. Downs, C. Santiago, R.A. Allingham, D.C. Musch, J.E. Richards, S.E. Moroi; Do ß2–Adrenergic Receptor Single Nucleotide Polymorphisms and Haplotypes Contribute to Aqueous Humor Flow Variations in Humans? . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3386.
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Intraocular pressure (IOP) fluctuation contributes to glaucoma progression. Since aqueous humor flow is a determinant of IOP, our objectives were to determine the following: 1) whether ß2–adrenergic receptor (AR) single nucleotide polymorphisms (SNPs) and haplotypes contribute to flow variation, and 2) whether the ß2–AR gene is a glaucoma susceptibility locus.
Flow was measured by fluorophotometry in the morning and nighttime in normal human subjects. Differences in flow and concordance of individual morning and nighttime flows were analyzed. The ß2–AR SNPs and haplotypes were determined by sequencing and allele–specific polymerase chain reaction (PCR) combined with restriction enzyme digestion.
Flow was similar between eyes within a subject (n = 28). Using one eye from each subject, the average morning flow was 3.12 + 1.09 µl/min, which decreased significantly to 1.59 + 0.58 µl/min at nighttime (p–value < 0.0001). For both time periods, the flow data were normally distributed. A new finding is concordance of individual flow in the morning and nighttime. When flow variation is largest the in morning, ß2–AR haplotypes appear to contribute to this variation. In a case–control study stratified by race and disease (White control, n = 150; Black control, n = 158; vs. White primary open–angle glaucoma, n = 138; Black primary open–angle glaucoma, n = 143), there were no statistically significant differences in ß2–AR alleles and haplotypes between controls and POAG cases whether analyzed together or by race. Previously described race–based differences in ß2–AR allele frequencies and haplotypes were found.
We have shown two new findings regarding flow variation. First, individuals show concordance of flow in morning and nighttime. Second, when the flow distribution is large in the morning, that ß2–AR haplotypes seem to contribute to this variation. Since the ß2–AR gene is not a glaucoma susceptibility locus, we can determine the role of ß2–AR and other potential candidate genes on IOP variation, which is an important risk factor for glaucoma progression.
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