Evaluation of FGF10 as a candidate gene for high myopia in a Han Chinese population

Abstract

BackgroundFibroblast growth factor 10 (FGF10) is implicated in the growth and development of the eye. Four singles nucleotide polymorphisms (SNPs) in the FGF10 gene (including rs1384449, rs339501, rs12517396 and rs10462070) were found to be associated with extreme myopia (EM, refractive error ≤ − 10.0 diopters) in Japanese and Chinese Taiwan population. This case-control association study was conducted to explore the relationship between these four SNPs and high myopia in a western Chinese population.MethodsA total of 869 high myopia patients (HM, including 485 EM patients) and 899 healthy controls were recruited. These four SNPs were genotyped using the ABI SNaPshot method. Five genetic models (allelic, homozygous, heterozygous, dominant, and recessive) were applied to further evaluate the possible correlation between the SNPs and high myopia. The linkage-disequilibrium block (LD) structure was tested by Haploview Software.ResultsIn our study, no statistically significant differences were found between HM/EM patients and controls after Bonferroni multiple-correction (P > 0.05) in the allele frequencies of these four SNPs in the FGF10 gene. We further found that rs12517396AA and rs10462070GG carriers showed a decreased risk of HM/EM compared with rs12517396AC + CC and rs10462070GA + AA carriers (P = 0.045, OR = 0.366; P = 0.021, OR = 0.131; P = 0.03, OR = 0.341; P = 0.015, OR = 0.122; respectively). Additionally, rs12517396AA and rs10462070GG carriers showed the same decreased risk of HM/EM compared with rs12517396CC and rs10462070AA carriers (P = 0.048, OR = 0.370; P = 0.023, OR = 0.133; P = 0.032, OR = 0.346; P = 0.017, OR = 0.126). However, these significant associations between rs12517396/rs10462070 and HM/EM disappeared after Bonferroni multiple-correction (P > 0.05).ConclusionOur findings indicate that rs12517396 and rs10462070 had marginal association with HM and EM. The other two common polymorphisms in FGF10 unlikely have significant effects in the genetic predisposition to HM/EM in western Chinese population. Further replication studies are needed to validate our findings in both animal models and human genetic epidemiologic studies.

Phenotypic spectrum of FGF10-related disorders: a systematic review

“…Myopia is one of the most common eye abnormalities identified in humans ( Holden et al, 2016 ). High myopia, characterized by refractive error (RE) ≤ -6 diopters (D) or axial length (AL) ≥ 26 mm ( Kempen et al, 2004 ; Pan, Ramamurthy & Saw, 2012 ), and extreme myopia, with RE ≤−10.00 D or AL ≥ 30 mm, can lead to pathological changes in the eye, and disturbing vision ( Jiang et al, 2019 ). High myopia can cause glaucoma, retinal detachment, or macular degeneration, resulting in visual impairment ( Saw et al, 2005 ; Jiang et al, 2019 ).…”

“…One of the most important FGF ligands is fibroblast growth factor 10 (FGF10), which plays an essential role in airway branching ( Jones, Chong & Bellusci, 2020 ), functioning of the cardiovascular system ( Itoh et al, 2016 ), and development of the kidney, cecum, thymus, trachea, prostate, mammary gland, adipose tissue, and limb ( Itoh, 2016 ). Pathogenic variants in FGF10 can cause craniofacial defects ( Prochazkova et al, 2018 ), lung disorders ( Vincent et al, 2019 ), myopia ( Jiang et al, 2019 ), limb ( Ohuchi et al, 2000 ) or genitourinary system anomalies ( Milunsky et al, 2006 ), and heart defects ( Itoh et al, 2016 ). Alterations in FGF10 have been associated with cancers, including breast or pancreatic cancer ( Dankova et al, 2017 ; Ndlovu et al, 2018 ).…”

Association of FGF10 polymorphism of rs339501 with myopia: A systematic review and meta-analysis

“…The full text of the remaining 7 studies were reviewed, during which, 1 article was excluded after full-text reading for replicate data. Finally, our meta-analysis included 6 studies(Figure 1) [14][15][16][17][18][19]. Among these studies, ve studies were conducted in China [14][15][16][17]19], one of them in Japan [18], and one of them were con ned to Children [14].…”

“…Finally, our meta-analysis included 6 studies(Figure 1) [14][15][16][17][18][19]. Among these studies, ve studies were conducted in China [14][15][16][17]19], one of them in Japan [18], and one of them were con ned to Children [14]. The meta-analysis included 4339 cases and 4652 controls in total.…”

“…Thereafter, several studies were also conducted to verify this association. Some of them con rmed that FGF10 rs339501 would increase the risk of high myopia or extreme myopia [14,[16][17] while Yoshida et al [18] reached the conclusion that the A allele of rs339501 is linked to a higher risk of developing extreme myopia in a Japanese population, what's more, Jiang L et al [19] couldn't nd a signi cant association. Therefore, we performed a meta-analysis to investigate the relationship between myopia and the rs339501 polymorphism of FGF10 gene.…”