Multilocus genetic risk score for diabetic retinopathy in the Han Chinese population of Taiwan.
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ABSTRACT:
SUBMITTER: Liao WL
PROVIDER: S-EPMC6162301 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
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Project description:This study aimed to explore the association of insulin-like growth factor 1 gene (IGF1) polymorphisms with diabetic retinopathy (DR) in a Chinese Han population.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Genotype frequencies were compared by chi-square test. Odds ratio (OR) with 95% confidence interval (95%CI) was calculated to express the risk intensity of DR. Linkage disequilibrium between IGF1 polymorphisms was analyzed by Haploview. Serum IGF1 concentration was measured by enzyme-linked immunosorbent assays (ELISA) and assessed by student's t test.AG genotype of rs6218 and TT genotype of rs35767 were significantly associated with the elevated risk of DR (rs6218: OR=1.77, P=0.04; rs35767: OR=2.32, P=0.03) and type II diabetes mellitus (T2DM) (rs6218: OR=1.92, P=0.00. rs35767: OR=2.29, P=0.02). Only T allele of rs35767 significantly increased the risk of DR (OR=1.45, P=0.04), however, rs6218 (OR=1.92, P=0.00), rs35767 (OR=0.02, P=0.02) and rs5742612 (OR=2.21, P=0.04) showed obvious association with T2DM. Haplotypes were only associated with T2DM, but not DR. Minor allele homozygote of rs35767 was obviously correlated with serum IGF1 level.IGF1 rs6218 and rs35767 polymorphisms contribute to the risk of DR. IGF1 rs35767 polymorphism may participate in the regulation of serum IGF1 concentration in DR.
| S-EPMC5675691 | biostudies-literature
Project description:We evaluated whether genetic information could offer improvement on risk prediction of diabetic nephropathy (DN) while adding susceptibility variants into a risk prediction model with conventional risk factors in Han Chinese type 2 diabetes patients. A total of 995 (including 246 DN cases) and 519 (including 179 DN cases) type 2 diabetes patients were included in derivation and validation sets, respectively. A genetic risk score (GRS) was constructed with DN susceptibility variants based on findings of our previous genome-wide association study. In derivation set, areas under the receiver operating characteristics (AUROC) curve (95% CI) for model with clinical risk factors only, model with GRS only, and model with clinical risk factors and GRS were 0.75 (0.72-0.78), 0.64 (0.60-0.68), and 0.78 (0.75-0.81), respectively. In external validation sample, AUROC for model combining conventional risk factors and GRS was 0.70 (0.65-0.74). Additionally, the net reclassification improvement was 9.98% (P = 0.001) when the GRS was added to the prediction model of a set of clinical risk factors. This prediction model enabled us to confirm the importance of GRS combined with clinical factors in predicting the risk of DN and enhanced identification of high-risk individuals for appropriate management of DN for intervention.
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Project description:More than 30 independent single-nucleotide polymorphisms (SNPs) have been associated with Alzheimer's disease (AD) risk by genome-wide association studies (GWAS) in European. We aimed to confirm these SNPs in Chinese Han and investigate the utility of these genetic markers. We randomly divided 459 sporadic AD (SAD) patients and 751 cognitively normal controls into two sets (discovery and testing). Thirty-three SAD risk-associated SNPs were firstly tested in the discovery set. Significant SNPs were used to calculate genetic risk score (GRS) in the testing set. Predictive performance of GRS was evaluated using the area under the receiver operating characteristic curve (AUC). In the discovery set, 6 SNPs were confirmed (P = 7.87 x 10(-11)~0.048), including rs9349407 in CD2AP, rs11218343 in SORL1, rs17125944 in FERMT2, rs6859 in PVRL2, rs157580 and rs2075650 in TOMM40. The first three SNPs were associated with SAD risk independent of APOE genotypes. GRS based on these three SNPs were significantly associated with SAD risk in the independent testing set (P = 0.002). The AUC for discriminating cases from controls was 0.58 for GRS, 0.60 for APOE, and 0.64 for GRS and APOE. Our data demonstrated that GRS based on AD risk-associated SNPs may supplement APOE for better assessing individual risk for AD in Chinese.
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Project description:AimTo identify the contribution of CDKAL1 to the development of diabetic retinopathy (DR) in Chinese population.MethodsA case-control study was performed to investigate the genetic association between DR and polymorphic variants of CDKAL1 in Chinese Han population with type 2 diabetes mellitus (T2DM). A well-defined population with T2DM, consisting of 475 controls and 105 DR patients, was recruited. All subjects were genotyped for the genetic variant (rs10946398) of CDKAL1. Genotyping was performed by iPLEX technology. The association between rs10946398 and T2DM was assessed by univariate and multivariate logistic regression (MLR) analysis.ResultsThere were significant differences in C allele frequencies of rs10946398 (CDKAL1) between control and DR groups (45.06% versus 55.00%, P<0.05). The rs10946398 of CDKAL1 was found to be associated with the increased risk of DR among patients with diabetes.ConclusionOur findings suggest that rs10946398 of CDKAL1 is independently associated with DR in a Chinese Han population.
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Project description:The levels of cytokines, inflammatory cells, and angiogenic factors increase following diabetic retinopathy (DR), and the association between interleukin-10 (IL-10) gene rs1800896 polymorphism (IL-10 -1082G/A polymorphism) and DR in different populations has been extensively studied. However, the findings are conflicting, and there is no relevant research in Chinese subjects. Therefore, this case-control study involving 327 cases (type 2 diabetes patients with proliferative DR (PDR)) and 461 controls (type 2 diabetes patients without DR) was conducted to address the relationship between IL-10 gene rs1800896 polymorphism and risk of PDR in Chinese population. Genotyping was performed using PCR-based restriction fragment length polymorphism (PCR-RFLP) assay. It was found that GG genotype or G allele of the IL-10 gene rs1800896 polymorphism was associated with decreased risk for PDR. In conclusion, IL-10 gene rs1800896 polymorphism decreases the risk of PDR.
| S-EPMC6470408 | biostudies-literature
Project description:BackgroundConsidering the involvement of genetics in migraine pathogenesis in diverse ethnic populations, genome-wide association studies (GWAS) are being conducted to identify migraine-susceptibility genes. However, limited surveys have focused on the onset age of migraine (AoM) in Asians. Therefore, in this study, we aimed to identify the susceptibility loci of migraine considering the AoM in an Asian population.MethodsWe conducted a GWAS in 715 patients with migraine of Han Chinese ethnicity, residing in Taiwan, to identify the susceptibility genes associated with AoM. Based on our standard demographic questionnaire, the population was grouped into different subsets. Single-nucleotide polymorphism (SNP) associations were examined using PLINK in different AoM onset groups.ResultsWe discovered eight novel susceptibility loci correlated with AoM that reached the GWAS significance level in the Han Chinese population. First, rs146094041 in ESRRG was associated with AoM [Formula: see text] 12 years. The other SNPs including rs77630941 in CUX1, rs146778855 in CDH18, rs117608715 in NOL3, rs150592309 in PRAP1, and rs181024055 in NRAP were associated with the later AoM.ConclusionsTo our knowledge, this is the first GWAS to investigate the AoM in an Asian Han Chinese population. Our newly discovered susceptibility genes may have prospective associations with migraine pathogenesis.
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Project description:Genome-wide association studies (GWAS) have reported that the polymorphism rs5219 of the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) is associated with type 2 diabetes mellitus (T2DM). Given that diabetic retinopathy (DR) is one of the most common microvascular complications of T2DM, GWAS have identified a number of potential susceptibility genes for DR. However, only a fraction of them have been replicated in different studies and show consistent genetic associations with the occurrence of DR. The aim of the present study was to investigate whether common variants of KCNJ11 confer DR in a cohort of the Chinese Han population.A case-control study of 580 T2DM patients, including 105 T2DM with DR and 475 T2DM without DR was performed. A single nucleotide polymorphism (SNP) of KCNJ11 (rs5219) was genotyped, and its association with DR was explored using a dominant genetic model. Genotyping was performed by iPLEX technology. Univariate and multivariate logistic regression (MLR) analysis controlling for confounders was conducted to evaluate the association between rs5219 and DR.The A allele frequency of rs5219 was significantly higher in DR patients than that in the patients without DR (49.01% versus 38.68%, P <0.05). We found the minor A allele could increase the risk to develop DR (ORint = 1.58, 95% CI: 1.139 to 2.192 for allele and P = 0.006, ORint =1.607, 95% CI: 1.267 to 2.038 for genotype and P <0.001) in the Chinese Han population.Our findings provided evidence that KCNJ11 was associated with DR in Chinese Han patients with T2DM.
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Project description:The aim of this study was to investigate the association of three single nucleotide polymorphisms in the erythropoietin gene polymorphisms with diabetic retinopathy and additional role of gene-gene interaction on diabetic retinopathy risk. A total of 1193 patients (579 men, 614 women) with type 2 diabetes mellitus were selected, including 397 diabetic retinopathy patients and 796 controls (type 2 diabetes mellitus patients without diabetic retinopathy); the mean age of all participants was 56.7?±?13.9 years. Three single nucleotide polymorphisms were selected: rs507392, rs1617640, and rs551238. The t-test was used for comparison of erythropoietin protein level erythropoietin levels in patients having different erythropoietin genotypes. Logistic regression model was used to examine the association between three single nucleotide polymorphisms and diabetic retinopathy. Odds ratio (OR) and 95% confident interval (95% CI) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the impact of interaction among three single nucleotide polymorphisms on CVD risk. After covariates adjustment, the carriers of homozygous mutant of three single nucleotide polymorphisms have higher diabetic retinopathy risk than those with wild-type homozygotes, OR (95% CI) were 2.04 (1.12-2.35), 1.87 (1.10-2.41) and 1.15 (1.06-1.76), respectively. Generalized multifactor dimensionality reduction model indicated a significant three-locus model (p?=?0.0010) involving rs507392, rs1617640, and rs551238. Overall, the three-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. Subjects with TC or CC-TG or GG-AC or CC genotype have the highest diabetic retinopathy risk. In conclusion, our results support an important association of rs507392, rs1617640 and rs551238 minor allele of erythropoietin with increased diabetic retinopathy risk, and additional interaction among three single nucleotide polymorphisms.
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Project description:To investigate the association of C5 SNPs with proliferative diabetic retinopathy (PDR) of type 2 diabetes (T2D).A total of four C5 SNPs including rs2269067, rs7040033, rs1017119 and rs7027797 were genotyped in 400 PDR patients with T2D (cases) and 600 non- proliferative diabetic retinopathy PDR (NPDR) with T2D patients (controls) by using PCR-RFLP method. mRNA expression was examined by real-time PCR. Cytokine production was detected by ELISA.The frequency of GG genotype of C5 rs2269067 was significantly increased in cases compared with controls (Pc = 3.4 × 10(-5), OR = 1.87). And C5 mRNA expression was significantly increased in rs2269067 GG cases as compared with CG or CC cases (P = 0.003, P = 0.001, respectively). Moreover, the production of IL-6 was significantly increased in rs2269067 GG cases compared to CG cases or CC cases (P = 0.002, P = 0.001, respectively).C5 rs2269067 GG genotype confers risk for PDR of T2D in Chinese han population and is associated with an elevated C5 mRNA expression and an increased IL-6 production.
| S-EPMC4775016 | biostudies-literature
Project description:TRPM8 plays a key role in COPD. The development of pulmonary hypertension (PH) in COPD adversely affects survival and exercise capacity. Thus, the aim of this study was to evaluate the possible association between single nucleotide polymorphisms (SNPs) in TRPM8 and COPD or PH in COPD among the Chinese Han population. A total of 513 COPD patients and 506 controls were enrolled in the study. Six tag SNPs (tSNPs) were genotyped. The relationship between COPD or PH in COPD and the six tSNPs was evaluated using the ?2 test and genetic model analysis. In the rs9789398 polymorphism, the T/C genotype was associated with an increased risk for COPD (P=0.005). Under the assumption of models of inheritance, there was an association between the rs9789398 polymorphism and COPD. In the rs9789675 polymorphism, the G/A genotype was associated with an increased risk for COPD (P=0.021). Furthermore, by the ?2 test, we found that the minor allele "A" of rs9789675 (odds ratio [OR] =0.63, 95% confidence interval [CI], 0.42-0.97, P=0.034) and the minor allele "C" of rs9789398 (OR =1.59, 95% CI, 1.03-2.44, P=0.034) were associated with a decreased risk of PH in COPD in allele models. In genetic models, the genotypes "GA" and "AA" of rs9789675 were associated with a decreased risk of PH in COPD. The genotypes "TC" and "CC" of rs9789398 were associated with a decreased risk of PH in COPD. Moreover, "CG" of rs1004478 was significantly associated with a decreased risk of PH in COPD. There was a significant association between the five SNPs (rs2362290, rs9789675, rs9789398, rs1003540, and rs104478) in the TRPM8 gene and the risk of PH in COPD. Our findings indicated that rs9789398 in the TRPM8 gene was significantly associated with the risk of COPD in the Chinese Han population. Moreover, rs9789675, rs9789398, and rs1004478 were significantly associated with the risk of PH in COPD. This study provides a novel insight into COPD and PH in the development of COPD.
| S-EPMC5072571 | biostudies-literature