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Genetic variants on chromosome 1q41 influence ocular axial length and high myopia.

Fan Q, Barathi VA, Cheng CY, Zhou X, Meguro A, Nakata I, Khor CC, Goh LK, Li YJ, Lim W, Ho CE, Hawthorne F, Zheng Y, Chua D, Inoko H, Yamashiro K, Ohno-Matsui K, Matsuo K, Matsuda F, Vithana E, Seielstad M, Mizuki N, Beuerman RW, Tai ES, Yoshimura N, Aung T, Young TL, Wong TY, Teo YY, Saw SM - PLoS Genet. (2012)

Bottom Line: We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = -0.16 mm per minor allele, P(meta) =2.69 × 10(-10)).In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1.This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.

View Article: PubMed Central - PubMed

Affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

ABSTRACT
As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = -0.16 mm per minor allele, P(meta) =2.69 × 10(-10)). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) =0.75, 95% CI: 0.68-0.84, P(meta) =4.38 × 10(-7)) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.

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mRNA expression of ZC3H11B, SLC30A10, and LYPLAL1 in human tissues.Expression of mRNA for the three genes was examined in human brain, placenta, neural retina (retina), retinal pigment epithelium (RPE) and sclera from adult tissues, and retina/RPE and sclera from 24-week gestation fetal tissues using reverse transcription polymerase chain reaction (RT-PCR). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a housekeeping gene and was used as an internal control for the quantification of mRNA expression. NTC (No template control) served as a negative control with the use of water rather than cDNA during PCR.
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pgen-1002753-g003: mRNA expression of ZC3H11B, SLC30A10, and LYPLAL1 in human tissues.Expression of mRNA for the three genes was examined in human brain, placenta, neural retina (retina), retinal pigment epithelium (RPE) and sclera from adult tissues, and retina/RPE and sclera from 24-week gestation fetal tissues using reverse transcription polymerase chain reaction (RT-PCR). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a housekeeping gene and was used as an internal control for the quantification of mRNA expression. NTC (No template control) served as a negative control with the use of water rather than cDNA during PCR.

Mentions: The mRNA expression levels of ZC3H11B, SLC30A10 and LYPLAL1 were surveyed in 24-week human fetal and adult tissues using reverse-transcriptase polymerase chain reaction (RT-PCR). Whilst ZC3H11B and LYPLAL1 were found to be expressed across all the tissues including brain, placenta, neural retina, retina pigment epithelium (RPE) and sclera, the expression of ZC3H11B was more abundant compared to LYPLAL1 (Figure 3). SLC30A10 was expressed in all tissues but the adult sclera, analogous to observations made in other zinc transporters [21].


Genetic variants on chromosome 1q41 influence ocular axial length and high myopia.

Fan Q, Barathi VA, Cheng CY, Zhou X, Meguro A, Nakata I, Khor CC, Goh LK, Li YJ, Lim W, Ho CE, Hawthorne F, Zheng Y, Chua D, Inoko H, Yamashiro K, Ohno-Matsui K, Matsuo K, Matsuda F, Vithana E, Seielstad M, Mizuki N, Beuerman RW, Tai ES, Yoshimura N, Aung T, Young TL, Wong TY, Teo YY, Saw SM - PLoS Genet. (2012)

mRNA expression of ZC3H11B, SLC30A10, and LYPLAL1 in human tissues.Expression of mRNA for the three genes was examined in human brain, placenta, neural retina (retina), retinal pigment epithelium (RPE) and sclera from adult tissues, and retina/RPE and sclera from 24-week gestation fetal tissues using reverse transcription polymerase chain reaction (RT-PCR). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a housekeeping gene and was used as an internal control for the quantification of mRNA expression. NTC (No template control) served as a negative control with the use of water rather than cDNA during PCR.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369958&req=5

pgen-1002753-g003: mRNA expression of ZC3H11B, SLC30A10, and LYPLAL1 in human tissues.Expression of mRNA for the three genes was examined in human brain, placenta, neural retina (retina), retinal pigment epithelium (RPE) and sclera from adult tissues, and retina/RPE and sclera from 24-week gestation fetal tissues using reverse transcription polymerase chain reaction (RT-PCR). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a housekeeping gene and was used as an internal control for the quantification of mRNA expression. NTC (No template control) served as a negative control with the use of water rather than cDNA during PCR.
Mentions: The mRNA expression levels of ZC3H11B, SLC30A10 and LYPLAL1 were surveyed in 24-week human fetal and adult tissues using reverse-transcriptase polymerase chain reaction (RT-PCR). Whilst ZC3H11B and LYPLAL1 were found to be expressed across all the tissues including brain, placenta, neural retina, retina pigment epithelium (RPE) and sclera, the expression of ZC3H11B was more abundant compared to LYPLAL1 (Figure 3). SLC30A10 was expressed in all tissues but the adult sclera, analogous to observations made in other zinc transporters [21].

Bottom Line: We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = -0.16 mm per minor allele, P(meta) =2.69 × 10(-10)).In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1.This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.

View Article: PubMed Central - PubMed

Affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

ABSTRACT
As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = -0.16 mm per minor allele, P(meta) =2.69 × 10(-10)). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) =0.75, 95% CI: 0.68-0.84, P(meta) =4.38 × 10(-7)) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia.

Show MeSH
Related in: MedlinePlus