Sclera-related gene polymorphisms in high myopia

[[abstract]]Purpose: Transforming growth factor-beta 2 (TGF-beta 2), basic fibroblast growth factor (bFGF), and fibromodulin (FMOD) are important extracellular matrix components of the sclera and have been shown to be associated with the development of high myopia. Our aim was to examine the association between myopia and the polymorphisms within TGF-beta 2, bFGF, and FMOD. Methods: The study group comprised of patients (n=195; age range: 17-24 years) with a spherical equivalent of -6.5 diopters (D) or a more negative refractive error. The control group comprised of individuals (n=94; age range: 17-25 years) with a spherical equivalent ranging from -0.5 D to +1.0 D. The subjects with astigmatism over -0.75 D were excluded from the study. High resolution melting (HRM) genotyping and restriction fragment length polymorphism (RFLP) genotyping were used to detect single nucleotide polymorphisms (SNPs). The polymorphisms detected were TGF-beta 2 (rs7550232 and rs991967), bFGF (rs308395 and rs41348645), and FMOD (rs7543418). Moreover, a stepwise logistic regression procedure was used to detect which of the significant SNPs contributed to the main effects of myopia development. Results: There were significant differences in the frequency of the A allele and A/A genotype in TGF-beta 2 ( rs7550232; p=0.0178 and 0.03, respectively). Moreover, the haplotype distribution of haplotype 2 (Ht2; A/A) of TGF-beta 2 differed significantly between the two groups (p=0.014). The results of the stepwise logistic regression procedure revealed that TGF-beta 2 (rs7550232) contributed significantly to the development of high myopia. Conclusions: TGF-beta 2 is an important structure of sclera and might contribute to the formation of myopia. TGF-beta 2 (rs7550232) polymorphisms, A allele and A/A genotype, had a protective role against the development of high myopia

Association of the Lumican Gene Functional 3 '-UTR Polymorphism with High Myopia

[[abstract]]PURPOSE. The lumican gene (LUM) encodes a major extracellular component of the fibrous mammalian sclera. Alteration in the expression levels of extracellular matrix components may influence scleral shape, which in turn could affect visual acuity. Single-nucleotide polymorphisms (SNPs) in the LUM gene were determined in an investigation of whether LUM gene polymorphisms correlate with high myopia. METHODS. Sequences spanning all three exons, intron-exon boundaries, and promoter regions were determined in 50 normal individuals. Five SNPs were identified, one of which was found to be a newly identified polymorphism. Genomic DNA was prepared from peripheral blood obtained from 201 patients with high myopia and 86 control subjects. Genotypes of the SNPs -1554 T/C (rs3759223), -628 A/-(rs17018757), -59 CC/-(rs3832846), c. 601 T/C (rs17853500), and the novel SNP c. 1567 C>T were determined by polymerase chain reaction. RESULTS. Of the five SNPs, one showed a significant difference between patients and control subjects (c. 1567 C>T, P = 0.0016). Haplotype analysis revealed a significantly higher presence of polymorphisms in patients with myopia (P < 0.0001). Moreover, the c. 1567 T polymorphism was determined to have lower reporter gene activity than that of c. 1567 C. CONCLUSIONS. These observations suggest that LUM gene polymorphisms contribute to the development of high myopia. (Invest Ophthalmol Vis Sci. 2010; 51: 96-102) DOI: 10.1167/iovs.09-361

Muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia

[[abstract]]Purpose: Numerous studies, including those using animal models of myopia development and human clinical trials, have shown that the non-selective muscarinic antagonist atropine is effective in preventing the axial elongation that leads to myopia development. Among all of the muscarinic acetylcholine receptors (mAChRs), mAChR 1 (M1) was the most effective in preventing myopic eye change. Our specific aim in this study was to examine the association between high myopia and polymorphisms within the muscarinic acetylcholine receptors 1 gene (CHRM1). Methods: The participants comprised of a high myopia group (n=194; age range, 17-24 years) having a myopic spherical equivalent greater than 6.5 diopters (D) and a control group (n=109; age range, 17-25 years) having a myopic spherical equivalent less than 0.5 D. Genotyping was performed using an assay-on-demand allelic discrimination assay. Polymerase chain reaction (PCR) was performed using 96 well plates on a thermal cycler. The polymorphisms detected were S1 (CHRM1 rs11823728), S2 (CHRM1 rs544978), S3 (CHRM1 rs2186410), and S4 (CHRM1 rs542269). Results: There was a significant difference in the distribution of S2 and S4 between the high myopia and control groups (p=2.40 x 10(-6) and 2.38 x 10(-8), respectively). The odds ratios of AA genotype of S2 and GG genotype of S4 were both 0.08 (95% confidence interval [CI]: 0.02-0.29 and 0.02-0.36, respectively). Logistic regression test revealed S1, S2, and S4 CHRM1 as all being significant in the development of high myopia. Moreover, the distributions of haplotype 4 (Ht4; C/A/A/A) differed significantly between the two groups (p=3.4 x 10(-5), odds ratio: 0.1, 95% CI: 0.03-0.34). Conclusions: Our results suggest that the S2 and S4 polymorphisms of CHRM1 are associated with susceptibility for developing high myopia. S1, S2, and S4 CHRM1 had a co-operative association with high myopia

Signatures of strong correlation effects in resonant inelastic x-ray scattering studies on cuprates

Recently, spin excitations in doped cuprates have been measured using resonant inelastic x-ray scattering. The paramagnon dispersions show the large hardening effect in the electron-doped systems and seemingly doping independence in the hole-doped systems, with the energy scales comparable to that of the antiferromagnetic (AFM) magnons. This anomalous hardening effect and the lack of softening were partially explained by using the strong-coupling t−J model but with a three-site term [Nat. Commun. 5, 3314 (2014)], although the hardening effect is already present even without the latter. By considering the t−t′−t"−J model and using the slave-boson mean-field theory, we obtain, via the spin-spin susceptibility, the spin excitations in qualitative agreement with the experiments. The doping-dependent bandwidth due to the strong correlation physics is the origin of the hardening effect. We also show that dispersions in the AFM regime, different from those in the paramagnetic (PM) regime, hardly vary with dopant density. These excitations are mainly collective in nature instead of particle-hole-like. We further discuss the interplay and different contributions of these two kinds of excitations in the PM phase and show that the dominance of the collective excitation increases with decreasing dopant concentrations