Dataset Information

Associations between CYP2C8 rs10509681 and rs11572080 gene polymorphisms and age-related macular degeneration.

ABSTRACT: BACKGROUND:Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in industrialized countries. Early symptoms of AMD include drusen and changes in retinal pigment epithelium. However, the etiology of AMD and drusen formation is not fully understood. Recent studies suggest that CYP2C8-related metabolic processes might play an important role in the development of AMD. The aim of our study is to investigate CYP2C8 rs10509681 and CYP2C8 rs11572080 genotype frequencies in patients with early AMD and to compare them with healthy controls. MATERIALS AND METHODS:The study enrolled 305 patients with early AMD and 300 healthy controls. The genotyping of CYP2C8 rs10509681 and CYP2C8 rs11572080 was carried out using the real-time PCR method. RESULTS:The analysis of studied CYP2C8 polymorphisms did not reveal any statistically significant differences between the AMD and the control groups. For the CYP2C8 rs10509681 gene polymorphism the distribution of T/T, T/C, and C/C genotypes was 83.3%, 16.7%, and 0% vs. 83.7%, 15.7%, and 0.7%, p = 0.343. For the CYP2C8 rs11572080 gene polymorphism the distribution of C/C, T/C and T/T and genotypes was 84.9%, 15.1%, and 0% vs. 82.3%, 17.3%, and 0.3%, p = 0.447. CONCLUSION:The study revealed that there were no statistically significant differences in the distribution of CYP2C8 rs10509681 and CYP2C8 rs11572080 genotypes in patients with early AMD and in healthy controls.

SUBMITTER: Liutkeviciene R

PROVIDER: S-EPMC5566945 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Associations between <i>CYP2C8</i> rs10509681 and rs11572080 gene polymorphisms and age-related macular degeneration.

Liutkevičienė Rasa R Sungailienė Ramunė R Vilkevičiūtė Alvita A Kriaučiūnienė Loresa L Vaitkienė Paulina P Chaleckis Romanas R Deltuva Vytenis Pranas VP

Acta medica Lituanica 20170101 2

<h4>Background</h4>Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in industrialized countries. Early symptoms of AMD include drusen and changes in retinal pigment epithelium. However, the etiology of AMD and drusen formation is not fully understood. Recent studies suggest that <i>CYP2C8</i>-related metabolic processes might play an important role in the development of AMD. The aim of our study is to investigate <i>CYP2C8</i> rs10509681 and <i>CYP2C8</ ...[more]

PMID: 28845124

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Project description:PurposeTo investigate whether insulin-like growth factor (IGF) axis genes, together with a novel dietary risk factor, the dietary glycemic index (dGI), and body mass index (BMI) affect the risk for age-related macular degeneration (AMD).MethodsThis case-control study involved 962 subjects originally recruited through the Age-Related Eye Disease Study (AREDS) Genetic Repository. After those with missing covariates or invalid calorie intake (n = 23), diabetes (n = 59), and non-Caucasian race (n = 16) were excluded, 864 participants were used, including 209 AREDS category 1 participants (control group), 354 category 2 or 3 participants (drusen group), and 301 category 4 participants (advanced AMD group). A total of 25 single-nucleotide polymorphisms (SNPs) selected from IGF-1 (n = 9), IGF-2 (n = 1), IGF binding protein 1 (IGFBP1; n = 3), IGFBP3 (n = 3), acid-labile subunit of IGFBP (IGFALS; n = 2), IGF1 receptor (IGF1R; n = 4), and IGF2R (n = 3) were genotyped. SNP-AMD associations were measured with genotype, allele χ(2) tests and Armitage's trend test. Odds ratios (OR), 95% confidence intervals (CIs), and SNP-exposure interactions were evaluated by multivariate logistic regression.ResultsOne SNP (rs2872060) in IGF1R revealed a significant association with advanced AMD (P-allele = 0.0009, P-trend = 0.0008; the significance level was set at 0.05/25 = 0.002 for multiple comparisons). The risk allele (G) in the heterozygous and homozygous states (OR, 1.67 and 2.93; 95% CI, 1.03-2.71 and 1.60-5.36, respectively) suggests susceptibility and an additive effect on AMD risk. Further stratification analysis remained significant for both neovascularization (OR, 1.49 and 2.61; 95% CI, 0.90-2.48 and 1.39-4.90, respectively) and geographic atrophy (OR, 2.57 and 4.52; 95% CI, 0.99-6.71 and 1.49-13.74, respectively). The G allele interaction analysis with BMI was significant for neovascularization (P = 0.042) but not for geographic atrophy (P = 0.47). No significant interaction was found with dGI.ConclusionsThese data suggest a role of IGF1R on the risk for advanced AMD in this group of subjects.

Project description:ObjectiveA genetic variant in the high-density lipoprotein (HDL) cholesterol pathway, hepatic lipase (LIPC), was discovered to be associated with advanced age-related macular degeneration (AMD) in a genome-wide association study. In this study, we evaluated whether LIPC is associated with serum lipids, and whether this gene and serum lipids are independently associated with AMD.DesignCase-control study.ParticipantsA total of 458 participants from the Progression Study of Macular Degeneration and the Age-Related Eye Disease Ancillary Biomarker Study, including 318 advanced AMD cases with either geographic atrophy (n = 123) or neovascular disease (n = 195) and 140 controls.MethodsParticipants were genotyped for 8 variants associated with AMD: 2 CFH variants, C2, CFB, C3, CFI, the ARMS2/HTRA1 gene region, and LIPC. Fasting blood specimens were obtained at study onset, and serum levels of total cholesterol, low-density lipoprotein (LDL), HDL, and triglycerides were determined. Logistic and linear regression were used to evaluate associations between serum lipids, LIPC genotype, and AMD.Main outcome measuresLIPC and serum lipid associations with AMD.ResultsThe minor T allele of the LIPC gene was associated with a reduced risk of AMD (odds ratio, 0.4; 95% confidence interval, 0.2-0.9; P = 0.01, trend for number of T alleles, controlling for age and gender). Mean level of HDL was lower (P = 0.05) and mean level of LDL (P = 0.03) was higher in cases of advanced AMD compared with controls. Higher total cholesterol and LDL levels were associated with increased risk of AMD, with P for trend = 0.01 for both, in models controlling for environmental and genetic covariates. The T allele of LIPC was associated with higher levels of HDL, although LIPC was associated with advanced AMD independent of HDL level.ConclusionsThe HDL-raising allele of the LIPC gene (T) was associated with a reduced risk of AMD. Higher total cholesterol and LDL levels were associated with increased risk, whereas higher HDL levels tended to reduce the risk of AMD. The specific mechanisms underlying the association between AMD and LIPC require further investigation.

Project description:PurposeTenomodulin (TNMD) is located in the X-chromosome encoding a putative angiogenesis inhibitor which is expressed in retina. Associations of single nucleotide polymorphisms of TNMD with the prevalence of age-related macular degeneration (AMD) were examined.MethodsSix markers covering 75% of the common sequence variation in the coding region of TNMD and 10 kb up- and downstream were genotyped in a sample consisting of 89 men and 175 women with exudative AMD, 18 men and 25 women with atrophic AMD, and 55 men and 113 women without AMD. All participants were over 65 years old and did not have diabetes mellitus. Due to the chromosomal locus, the association of genotypes with AMD was assessed genderwise.ResultsThree markers, rs1155974, rs2073163, and rs7890586, were associated with a risk of AMD in women. In comparison to women with other genotypes, the women who were homozygous for the minor allele (genotypes rs1155974-TT or rs2073163-CC) had 2.6 fold (p=0.021) or 1.9 fold (p=0.067) risk for having AMD, respectively. These differences were due to the unequal prevalence of exudative AMD. In comparison to women who were homozygous for the major alleles, the women with rs1155974-TT genotype had a 2.8 fold risk (p=0.021 in additive model; p=0.022 in recessive model) for exudative AMD, and the women with rs2073163-CC genotype had a 1.8 fold risk (p=0.09 in additive model; p=0.038 in recessive model). Furthermore, women carrying the rare rs7890586-AA genotype had a significantly smaller risk for having AMD than women with the other genotypes (odds ratio 0.083; p=0.001 in recessive model), but due to the low frequency of this genotype, this finding must be interpreted cautiously. The false discovery rate was <10% for all of the aforementioned results.ConclusionsOn the basis of the putative antiangiogenic role of TNMD and the present genetic associations of TNMD with AMD in women, we suggest that TNMD could be a novel candidate gene for AMD. These results should be confirmed in further studies.

Project description:PurposeA nonsynonymous coding variant in the manganese superoxide dismutase (SOD2) gene (V16A, rs4880) has been implicated in neovascular age-related macular degeneration (AMD). However, the findings have been inconsistent. Two studies in Japanese populations reported an opposite direction of association of the same allele at the V16A variant, whereas one study in a Northern Irish population found no effect of the variant on the risk of developing neovascular AMD. To address these apparently contradictory reports, we validated the association in a Japanese population.MethodsIn a Japanese population, we genotyped the V16A variant in 116 neovascular AMD patients, 140 polypoidal choroidal vasculopathy (PCV) patients, and 189 control participants. This association was also tested in a population of PCV participants to avoid variable findings across studies due to underlying sample heterogeneity and because disease phenotype was not well described in previous studies. We analyzed a tagging single nucleotide polymorphism (SNP) in addition to the V16A variant to capture all common SOD2 variations verified by the HapMap project. Genotyping was conducted using TaqMan technology. Associations were tested using single-SNP and haplotype analyses as well as a meta-analysis of the published literature. Population stratification was also evaluated in our study population.ResultsWe found no detectable association of the V16A variant or any other common SOD2 variation with either neovascular AMD or PCV, as demonstrated by both single-SNP and haplotype analyses. Population structure analyses precluded stratification artifacts in our study cohort. A meta-analysis of the association between the V16A variant and neovascular AMD also failed to detect a significant association.ConclusionsWe found no evidence to support the role of any common SOD2 variations including the V16A variant in the susceptibility to neovascular AMD or PCV. Our study highlights the importance and difficulty in replicating genetic association studies of complex human diseases.

Dataset Information

Associations between CYP2C8 rs10509681 and rs11572080 gene polymorphisms and age-related macular degeneration.

Publications

Associations between <i>CYP2C8</i> rs10509681 and rs11572080 gene polymorphisms and age-related macular degeneration.

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