Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children

• Published in: British journal of ophthalmology Vol. 107; no. 8; pp. 1216 - 1222
• Main Authors: Lu, Shi Yao, Zhang, Xiu Juan, Wang, Yu Meng, Yuan, Nan, Kam, Ka Wai, Chan, Poemen P, Tam, Pancy OS, Yip, Wilson WK, Young, Alvin L, Tham, Clement C, Pang, Chi Pui, Yam, Jason C, Chen, Li Jia
• Format: Journal Article
• Language: English
• Published: BMA House, Tavistock Square, London, WC1H 9JR BMJ Publishing Group Ltd 01.08.2023; BMJ Publishing Group LTD
• Subjects: Adult; Age groups; Child; child health (paediatrics); Data analysis; Drug dosages; Ears & hearing; Female; genetics; Genotype; Glaucoma; Glaucoma, Open-Angle; Homeodomain Proteins; Humans; imaging; Laboratory science; Male; Males; Mutation; Nerve Fibers; optic nerve; Pediatrics; Polymorphism, Single Nucleotide; Retina; Tomography, Optical Coherence; Trans-Activators; Variance analysis; Hong Kong China; California; United States > US; China; Germany; genetics; child health (paediatrics); imaging; optic nerve; glaucoma
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjophthalmol-2021-319756

PurposeAssociation of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications.Methods2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression.ResultsSNPs rs33912345 (p=7.7×10−4) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8–9 year-old group for rs33912345 (p=5.2×10−4) and rs10483727 (p=3.3×10−4). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (β=1.66; p=0.0059), but not rs33912345-C (β=1.31; p=0.052) or rs10483727-T (β=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL.ConclusionsBoth rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood.