Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort.
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ABSTRACT:
SUBMITTER: Metlapally R
PROVIDER: S-EPMC2941166 | biostudies-literature | 2010 Sep
REPOSITORIES: biostudies-literature
Publications
Genetic association of insulin-like growth factor-1 polymorphisms with high-grade myopia in an international family cohort.
Metlapally Ravikanth R Ki Chang-Seok CS Li Yi-Ju YJ Tran-Viet Khanh-Nhat KN Abbott Diana D Malecaze Francois F Calvas Patrick P Mackey David A DA Rosenberg Thomas T Paget Sandrine S Guggenheim Jeremy A JA Young Terri L TL
Investigative ophthalmology & visual science 20100430 9
<h4>Purpose</h4>Evidence from human myopia genetic mapping studies (MYP3 locus), modulated animal models, and observations of glycemic control in humans suggests that insulin-like growth factor (IGF)-1 plays a role in the control of eye growth. This study was conducted to determine whether IGF-1 polymorphisms are associated with myopia in a large, international dataset of Caucasian high-grade myopia pedigrees.<h4>Methods</h4>Two hundred sixty-five multiplex families with 1391 subjects participat ...[more]
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Project description:PurposeThe purpose of this study was to determine whether genetic variants in the insulin-like growth factor-1 (IGF-1) gene were associated with high myopia in the Chinese population.MethodsA case-control association study of 421 unrelated Chinese patients with high myopia and 401 control subjects matched in ethnicity and gender was undertaken. Genomic DNA was prepared from peripheral blood. All individuals were genotyped for 7 tag single nucleotide polymorphisms (tSNPs) across the IGF-1 gene region. Genotypic distribution was tested for Hardy-Weinberg equilibrium. The genotype and allele frequencies were evaluated using the χ(2) tests. Bonferroni corrections for multiple comparisons were performed.ResultsThe polymorphism of rs12423791 showed positive association with extreme myopia (p(allel)=0.006 and p(allel1 recessive model)=0.004, respectively) after Bonferroni correction for multiple testing and the haplotype GC of rs5742629-rs12423791 was also associated with extreme myopia (p=0.033) after 50,000 permutations for multiple comparisons.ConclusionsThe polymorphism of rs12423791 in IGF-1 may be associated with extreme myopia in the Chinese population and should be investigated further.
| S-EPMC3324364 | biostudies-literature
Project description:ObjectiveTo evaluate the association of insulin-like growth factor 1 gene rs12423791 and rs6214 polymorphisms with high myopia.MethodsAn electronic search was conducted on PubMed, Embase, the Cochrane Library and the Chinese Biological Abstract Database for articles published prior to May 6, 2014. A meta-analysis was performed using Revman 5.1 and Stata 12.0, and the odds ratios with 95% confidence intervals were calculated in fixed or random effects models based on the results of the Q test. The subgroup analysis was conducted on the basis of the various regions, the sensitivity analysis was also performed to evaluate the stability of the results, and the publication bias was evaluated by a funnel plot and Egger's linear regression analysis.ResultsThis comprehensive meta-analysis included 2808 high myopia patients and 2778 controls from five unrelated studies. The results demonstrated that the significant association was not present in any genetic models between IGF-1 rs12423791 or rs6214 and high myopia. However, subgroup analysis indicated that rs12423791 polymorphism was associated with high myopia in the Chinese populations in the allelic contrast model (C vs. G: OR=1.24, 95% CI=1.04-1.48 in the fixed-effects model), the dominant model (CC+CG vs. GG: OR=1.40, 95% CI=1.16-1.69 in the fixed-effects model), and the codominant model (CG vs. GG: OR=1.37, 95% CI= 1.12-1.68 in the fixed-effects model). Additionally, none of the individual studies significantly affected the association between IGF-1 rs12423791 and high myopia, according to sensitivity analysis.ConclusionThis meta-analysis shows that IGF-1 rs12423791 or rs6214 gene polymorphism is not associated with high myopia.
| S-EPMC4468052 | biostudies-literature
Project description:Several nonsyndromic high-grade myopia loci have been mapped primarily by microsatellite markers and a limited number of pedigrees. In this study, whole-genome linkage scans were performed for high-grade myopia, using single nucleotide polymorphisms (SNPs) in 254 families from five independent sites.Genomic DNA samples from 1411 subjects were genotyped (Linkage Panel IVb; Illumina, San Diego, CA). Linkage analyses were performed on 1201 samples from 10 Asian, 12 African-American, and 221 Caucasian families, screening for 5744 SNPs after quality-control exclusions. Two disease states defined by sphere (SPH) and spherical equivalence (SE; sphere+cylinder/2) were analyzed. Parametric and nonparametric two-point and multipoint linkage analyses were performed using the FASTLINK, HOMOG, and MERLIN programs. Multiple stratified datasets were examined, including overall, center-specific, and race-specific. Linkage regions were declared suggestive if they had a peak LOD score >or= 1.5.The MYP1, MYP3, MYP6, MYP11, MYP12, and MYP14 loci were replicated. The novel region q34.11 on chromosome 9 (max NPL= 2.07 at rs913275) was identified. Chromosome 12, region q21.2-24.12 (36.59 cM, MYP3 locus) showed significant linkage (peak HLOD = 3.48) at rs337663 in the overall dataset by SPH and was detected by the Duke, Asian, and Caucasian subsets as well. Potential shared interval was race dependent-a 9.4-cM region (rs163016-rs1520724) driven by the Asian subset and a 13.43-cM region (rs163016-rs1520724) driven by the Caucasian subset.The present study is the largest linkage scan to date for familial high-grade myopia. The outcomes will facilitate the identification of genes implicated in myopic refractive error development and ocular growth.
| S-EPMC3696634 | biostudies-literature
Project description:PURPOSE: To investigate whether genetic variations in the insulin-like growth factor 1 (IGF-1) gene are associated with high myopia in Japanese. METHODS: A total of 1,339 unrelated Japanese patients with high myopia (axial length ?26 mm in both eyes) and two independent control groups were evaluated (334 cataract patients without high myopia and 1,194 healthy Japanese individuals). The mean axial length (mm±SD) in the case group was 29.18±1.85 mm, and the mean spherical equivalent (D±SD) of the phakic eyes was -12.69±4.54 D. We genotyped five tagging single nucleotide polymorphisms (SNPs) in IGF-1: rs6214, rs978458, rs5742632, rs12423791, and rs2162679. Chi-square tests for trend, multivariable logistic regression, and haplotype regression analysis were conducted. RESULTS: We found no significant association between the IGF-1 SNPs and high or extreme myopia (axial length ?28 mm in both eyes, 837 subjects) in the additive model, even when compared with the cataract and general population controls, with or without adjustments for age and sex. The evaluation using dominant and recessive models also did not reveal any significant associations. The haplotype analysis with a variable-sized sliding-window strategy also showed a lack of association of IGF-1 SNPs with high or extreme myopia. CONCLUSIONS: The results of the present study using a Japanese subset do not support the proposal that the IGF-1 gene determines susceptibility to high or extreme myopia in Caucasians and Chinese. Further studies are needed to confirm our reports in other populations and to identify the underlying genetic determinants of these ocular pathological conditions.
| S-EPMC3668686 | biostudies-literature
Project description:PurposeThe fibroblast growth factor 10 (FGF10) gene polymorphism rs339501 was previously reported to be associated with high myopia in a Chinese population. In the present study, we investigated whether FGF10 polymorphisms are associated with extreme myopia in a Japanese population as well.MethodsA total of 433 Japanese patients with extreme myopia (≤ -10.00 diopters) and 542 Japanese healthy controls (+1.50 to -1.50 diopters) were recruited. We genotyped seven tagging single-nucleotide polymorphisms (SNPs), including rs339501, in FGF10. We also performed an imputation analysis to evaluate the potential association of ungenotyped FGF10 SNPs, and 34 SNPs were imputed.ResultsIt was found that rs339501 and rs12517396 exhibited the strongest association with extreme myopia (p=3.9 × 10⁻⁴, corrected p [Pc]=0.0030). A significant association was also observed for rs10462070 (p=6.5 × 10⁻⁴, Pc=0.0059). These three SNPs were in strong linkage disequilibrium (D' ≥0.99, r² ≥0.96). However, the frequency of the A allele of rs339501 was increased in cases compared to controls, which differs from the increased frequency of the G allele in cases in the previous Chinese population.ConclusionsThree FGF10 SNPs in complete linkage disequilibrium--rs339501, rs12517396, and rs10462070--were associated with extreme myopia in the Japanese population, and the risk allele of rs339501 differed from the previous Chinese population. Therefore, these three SNPs may not be an important risk factor for susceptibility to extreme myopia. Further studies are needed to elucidate the possible contribution of the FGF10 region in the development of extreme myopia.
| S-EPMC3834595 | biostudies-literature
Project description:This study was designed to analyze the association between the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis gene polymorphisms and short stature in Chinese children.181 growth hormone deficiency (GHD) patients and 206 normal stature controls were enrolled to attend this study. Five single-nucleotide polymorphisms in the GH receptor (GHR) and 5 SNPs within the GH-signaling pathway were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry. We conducted an association study between these SNPs and the risk of developing short stature. Linkage disequilibrium analysis was performed using Haploview software and the associations of the SNPs frequencies with short stature were analyzed using X2 tests.No significant difference was found in gender, weight, height, and BMI between the GHD and control groups, except that the age of GHD group was older than the control one. Allele and genotype frequencies were consistent with those expected from Hardy-Weinberg equilibrium. Compared with the controls, heterozygous genotype frequencies (CT) of rs12515480 and rs6873545 of GHR gene were significantly lower. Genotype frequencies of the other 8 SNPs did not show significant difference between these two groups. Considering a dominant model, an OR < 1 was observed for genotypes rs12515480 (OR = 0.532, P = 0.019) and rs6873545 (OR = 0.587, P = 0.017).The heterozygous genotypes of rs12515480 and rs6873545 of GHR gene were associated with decreased risk of GHD in Chinese children.
| S-EPMC5857343 | biostudies-literature
Project description:BackgroundSeveral studies have been conducted on the relationship between insulin-like growth factor 1 gene (IGF-1) rs35767 polymorphisms and cancer risk, but the results are conflicting. We performed a meta-analysis to investigate the relationship between IGF-1 rs35767 polymorphisms and cancer risk.MethodsEight studies (5 for IGF-1 rs35767 C>T and 3 for IGF-1 rs35767 A>G) with a total of 11,257 cases and 16,213 controls were included. The studies were about the association between IGF-1 rs35767 polymorphisms and cancer risk and acquired by searching PubMed, Embase, and Web of Science databases for articles published before January 20, 2019. STATA software was used to analyze the data and identify the strength of the association by using pooled-odds ratios (ORs) with corresponding 95% confidence intervals (CIs).ResultsNo significant associations were observed between the IGF-1 rs35767 C>T polymorphism and cancer risk in all genetic models. However, the IGF-1 rs35767 A>G polymorphism was significantly associated with increased cancer risk for all genetic models (G vs A: OR = 1.087, 95% CI: 1.036-1.141, Ph = .338; GG vs AA: OR = 1.272, 95% CI: 1.121-1.442, Ph = .359; AG vs AA: OR = 1.187, 95% CI: 1.043-1.351, Ph = .695; AG+GG vs AA: OR = 1.187, 95% CI: 1.043-1.351, Ph = .695; GG vs AA+AG: OR = 1.086, 95% CI: 1.025-1.151, Ph = .275). Begg and Egger tests showed that no publication bias existed.ConclusionOur findings indicated that the IGF-1 rs35767 A>G polymorphism might be a risk factor for cancer development. However, additional well-designed studies with sample sizes larger than ours need to be conducted in the future to verify our findings.
| S-EPMC6867772 | biostudies-literature
Project description:Hepatocyte growth factor (HGF) and hepatocyte growth factor receptor (C-MET) genes have previously been reported to be associated with myopia in Asian family-based and case-control association studies, respectively. We examined whether these genes were associated with myopia in a Caucasian family dataset biased towards high myopia.Participating families had at least one offspring with high myopia (< or = -5.00 diopters [D]). Genotyping was performed with tagging single nucleotide polymorphisms (SNPs) for each candidate gene using Taqman allelic discrimination assays. The data were analyzed with two family-based association methods, the pedigree disequilibrium test (PDT) and the association in the presence of linkage (APL) test. Analyses compared 1) high myopia (<-5.00 D), 2) mild to moderate myopia (-0.50 to -5.00 D), 3) any myopia (<-0.50 D) and 4) extreme high myopia (< or =-10.00 D) versus emmetropia using refractive error as either sphere (SPH) or spherical equivalent (SE=sphere + [cylinder/2]). Bonferroni correction was applied to adjust for multiple testing leading to significance levels of 0.0125 for HGF and 0.008 for C-MET. Two and three-marker sliding window haplotype association tests using APL were also performed for HGF markers. Significance levels for haplotype association testing were set at 0.01 for the global tests, and 0.007 for the three marker haplotype specific tests and 0.0125 for the two marker haplotype specific tests.A total of 146 multiplex families consisting of 649 Caucasian subjects were included. The HGF SNP, rs3735520 (APL p=0.002768 for SPH and 0.005609 for SE), and the haplotypes, rs2286194-rs3735520-rs17501108 (APL p=0.007403 for SPH and 0.062685 for SE) and rs12536657-rs2286194 (APL p=0.004219 for SPH and 0.00518 for SE), showed significant association with mild to moderate myopia versus emmetropia. A promising association between extreme high myopia and the HGF SNP, rs2286194, was also found (APL p=0.005763 for SPH and 0.004103 for SE). No evidence of association was found in the SNPs tested for C-MET.This study supports a strong association between the mild to moderate myopia group and the HGF SNP rs3735520 and the HGF haplotypes rs2286194-rs3735520-rs17501108 and rs12536657-rs2286194, and a moderate association of the extreme high myopia with rs2286194. C-MET polymorphism statistical associations with myopia in an Asian study were not replicated in our Caucasian cohort. HGF may be a potential myopia candidate gene for further investigation.
| S-EPMC2684748 | biostudies-literature
Project description:PURPOSE: Recent work has suggested that insulin-like growth factor 1 (IGF-1) gene polymorphisms are genetically linked with high-grade myopia (HM), which is a complex-trait eye disorder in which numerous candidate loci and genes are thought to play a role. We investigated whether the IGF-1 single nucleotide polymorphisms (SNPs) rs6214, rs10860860, and rs2946834 are associated with HM (?-6.0 diopters [D]) and any myopia (?-0.5 D) phenotype in Polish families. METHODS: Forty-two multiplex HM Polish families, of whom 127 had HM, participated in the study. All of the family members (n=306) underwent a detailed ophthalmic examination, including axial length measurements. The IGF-1 SNPs rs6214, rs10860860, and rs2946834 were evaluated by PCR-RFLP and direct sequencing methods. Both Family-Based Association Test (FBAT) and family-based Pedigree Disequilibrium Test (PDT) were used to examine the potential association of the IGF-1 SNPs rs6214, rs10860860, and rs2946834 with HM or any myopia. To determine the distribution of the HM-associated SNPs rs6214 and rs10860860, 543 unrelated individuals from the general Polish population were also analyzed. RESULTS: We found no significant association between the IGF-1 SNPs rs6214, rs10860860, and rs2946834 and HM or any myopia phenotype in Polish HM families. In the general Polish population, the minor allele frequencies of the SNPs rs6214 and rs10860860 did not deviate significantly from the distribution reported for European populations (p=0.629). In the FBAT analysis under the dominant model, the haplotype consisted of T allele of rs10860860, with C allele of rs2946834 of IGF-1 was found less frequently transmitted to HM individuals (p=0.0065), pointing to a nonassociated or protective haplotype. CONCLUSIONS: Our results do not support recent studies reporting an association of the SNPs rs6214, rs10860860, and rs2946834 in the IGF-1 gene with HM and any myopia phenotypes. Further replication studies involving other populations are needed to investigate the possible role of IGF-1 as a potential myopia candidate gene.
| S-EPMC3185023 | biostudies-literature
Project description:The insulin-like growth factor (IGF) axis plays an essential role in the development of the mammary gland. High circulating levels of IGF-I and of its major binding protein IGFBP3 have been related with increased mammographic density in Caucasian premenopausal women. Some common single nucleotide polymorphisms (SNPs) in genes of the IGF pathway have also been suggested to play a role in mammographic density. We conducted a cross-sectional study nested within the large Mexican ESMaestras cohort to investigate the relation between circulating levels of IGF-I, IGFBP-3, the IGF-I/IGFBP-3 ratio, five common SNPs in the IGF-1, IGFBP-3 and IGF-1R genes and mammographic density in 593 premenopausal Mexican women. Mean age at mammogram was 43.1 (standard deviation, SD = 3.7) years, and average body mass index (BMI) at recruitment was 28.5 kg/m(2). Mean percent mammographic density was 36.5% (SD: 17.1), with mean dense tissue area of 48.3 (SD: 33.3) cm(2) . Mean IGF-I and IGFBP-3 concentrations were 15.33 (SD: 5.52) nmol/l and 114.96 (SD: 21.34) nmol/l, respectively. No significant associations were seen between percent density and biomarker concentrations, but women with higher IGF-I and IGF-I/IGFBP-3 concentrations had lower absolute dense (p(trend) = 0.03 and 0.09, respectively) and nondense tissue areas (p(trend) < 0.001 for both parameters). However, these associations were null after adjustment by BMI. SNPs in specific genes were associated with circulating levels of growth factors, but not with mammographic density features. These results do not support the hypothesis of a strong association between circulating levels of growth hormones and mammographic density in Mexican premenopausal women.
| S-EPMC4487637 | biostudies-literature