Tetyana Zayats

COL1A1 and COL2A1 Genes and Myopia Susceptibility: Evidence of Association and Suggestive Linkage to the COL2A1 Locus

PURPOSEnCollagen involvement in myopia development via scleral remodeling is well-known. Recently, COL1A1 and COL2A1 gene polymorphisms were reported to be associated with high-grade and common myopia, respectively. This study was conducted to investigate whether these collagen genes are associated and/or genetically linked with myopia in large Caucasian family datasets.nnnMETHODSnHigh-grade myopia was defined as <or=-5.00 D. Two independent datasets comprising 146 (Duke) and 130 (Cardiff) families with high-grade myopia participated in the association study. Allelic discrimination assays were performed on tagging SNPs for COL1A1 and COL2A1. The pedigree disequilibrium test (PDT) and the association test in the presence of linkage (APL) were used for association analyses. Linkage analyses for COL2A1 locus markers were performed with the Fastlink and Merlin programs in conjunction with data obtained from our collaborative whole-genome linkage study (254 families).nnnRESULTSnSignificant association was identified between five SNPs (rs1034762, rs1635529, rs1793933, rs3803183, and rs17122571) of the COL2A1 locus and high-grade myopia (P < 0.045, minimum (min) P = 0.008) and with myopia status set at <or=-0.50 or -0.75 D (min P = 0.004) in the Duke dataset. The SNP rs1635529 also showed significant association in the Cardiff dataset (<or=-5.00 D, min P = 0.004; <or=-0.50 D, min P = 0.007). Linkage analyses showed suggestive linkage to the COL2A1 locus on 12q. No association was found between COL1A1 SNPs and any degree of myopia.nnnCONCLUSIONSnThe COL2A1 gene was associated with high-grade myopia in two independent Caucasian family datasets. COL1A1 gene polymorphisms were not associated with myopia in our dataset, indicating possible heterogeneity across different ethnicities.

Season of Birth, Daylight Hours at Birth, and High Myopia

PURPOSEnMandel et al recently reported that season of birth and daylight hours (photoperiod) at birth were associated with moderate and high levels of myopia in Israeli conscripts. We sought to investigate whether these associations were evident in subjects from the United Kingdom (UK).nnnDESIGNnRetrospective cross-sectional study.nnnPARTICIPANTSnThe study population comprised 74,459 subjects aged 18 to 100 years attending UK optometry practices for an eye examination.nnnMETHODSnData comprising non-cycloplegic spectacle prescription, sex, date of birth, and date of eye examination were collected from UK optometry practices. The average refractive error in fellow eyes was used to classify the degree of myopia in diopters (D) for each subject as follows: absent (>-0.75 D), low (-0.75 to -2.99 D), moderate (-3.00 to -5.99 D), or high (<-6.00 D). The average monthly hours of daylight for London, UK, were classified into 1 of 4 photoperiod categories, following Mandel et al. The odds ratio (OR) for each level of severity of myopia was calculated using multivariate logistic regression with age, sex, and either season of birth or photoperiod category as risk factors.nnnMAIN OUTCOME MEASURESnThe OR for season of birth and photoperiod category as potential risk factors for myopia.nnnRESULTSnSeason of birth was significantly associated with the presence of high myopia: Subjects born in summer or autumn were more likely to be highly myopic compared with those born in winter (summer OR=1.17; 95% confidence interval [CI], 1.05-1.30; P=0.006; autumn OR=1.16; 95% CI, 1.04-1.30; P=0.007). However, season of birth was not a significant risk factor for low or moderate myopia. Photoperiod category was weakly associated with low myopia (OR=0.94; 95% CI, 0.89-0.99; P=0.019), but with a direction of effect opposite to that observed by Mandel et al.nnnCONCLUSIONSnAs in Israel, a disproportionate number of UK high myopes were born in summer or autumn rather than in winter. However, unlike the situation in Israel, this association does not seem to be related to daylight hours during the postnatal period, implicating alternative physiologic influences that vary with season, such as birth weight.

Axes of astigmatism in fellow eyes show mirror rather than direct symmetry

Purpose:u2002 Most astigmats have a similar level of astigmatism in each eye. However, there is controversy over whether the astigmatic axes in fellow eyes typically show direct or mirror symmetry. We carried out a statistical analysis designed to address this issue.

Quality of DNA extracted from mouthwashes

Background A cost effective, safe and efficient method of obtaining DNA samples is essential in large scale genetic analyses. Buccal cells are an attractive source of DNA, as their collection is non-invasive and can be carried out by mail. However, little attention has been given to the quality of DNA extracted from mouthwashes. Methodology Mouthwash-derived DNA was extracted from 500 subjects participating in a genetic study of high myopia. DNA quality was investigated using two standard techniques: agarose gel electrophoresis and quantitative polymerase chain reaction (qPCR). Principal Findings Whereas the majority of mouthwash-derived DNA samples showed a single band of high molecular weight DNA by gel electrophoresis, 8.9% (95% CI: 7.1–10.7%) of samples contained only a smear of low-to-medium molecular weight, degraded DNA. The odds of DNA degradation in a subjects second mouthwash sample, given degradation of the first, was significantly greater than one (ORu200a=u200a3.13; 95% CI: 1.22–7.39; Fishers test Pu200a=u200a0.009), suggesting that DNA degradation was at least partially a subject-specific phenomenon. Approximately 12.4% (95% CI: 10.4–14.4%) of mouthwash-derived DNA failed to PCR amplify efficiently (using an ∼200 bp microsatellite marker). However, we found there was no significant difference in amplification success rate between DNA samples judged to be degraded or non-degraded by gel electrophoresis (Fishers test Pu200a=u200a0.5). Conclusions This study demonstrated that DNA degradation affects a significant minority of saline mouthwashes, and that the phenomenon is partially subject-specific. Whilst the level of degradation did not significantly prevent successful amplification of short PCR fragments, previous studies suggest that such DNA degradation would compromise more demanding applications.

Comment on 'A PAX6 gene polymorphism is associated with genetic predisposition to extreme myopia'

Comment on ‘A PAX6 gene polymorphism is associated with genetic predisposition to extreme myopia’

Lumican and muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia

Lumican and muscarinic acetylcholine receptor 1 gene polymorphisms associated with high myopia