Polymorphisms and genetic susceptibility of type 1 diabetes mellitus and celiac disease
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ABSTRACT:
SUBMITTER: Bastos M
PROVIDER: S-EPMC4659250 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
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Project description:Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.
| S-EPMC4127584 | biostudies-literature
Project description:BackgroundSolute carrier family 22 member 3 (SLC22A3) gene had been reported to be associated with the efficacy of metformin in type 2 diabetes mellitus (T2DM). However, few studies reported the relationship between SLC22A3 polymorphism and T2DM. The aim of this study was to investigate the association of SLC22A3 polymorphism and susceptibility to T2DM in Chinese population.MethodsWe identified SLC22A3 rs555754, rs3123636, rs3088442 genotypes of 450 T2DM patients and 220 healthy controls from the Chinese population. The association between SNPs of SLC22A3 and susceptibility of T2DM was evaluated.ResultsThe clinical characteristics were significantly different between T2DM patients and healthy controls. The polymorphisms of SLC22A3 rs555754 and rs3123636 were obviously associated with the susceptibility of T2DM which was adjusted for age, sex and BMI, while rs3088442 did not. And there was haplotype association of SLC22A3 rs3088442-rs3123636 with T2DM susceptibility.ConclusionSLC22A3 rs555754 and rs3123636 polymorphisms were associated with the susceptibility to T2DM in Chinese Han population. Large sample size studies would be required to verify this association.
| S-EPMC10278656 | biostudies-literature
Project description:BackgroundAlthough the association between HHEX, IGF2BP2, and FTO polymorphisms and the risk of GDM has been investigated in several studies, the findings have been inconsistent across different populations. The study aimed to investigate the association between genetic polymorphisms and GDM risk in a Chinese population.Methods502 control volunteers and 500 GDM patients were enrolled. IGF2BP2 rs11705701 and rs4402960, FTO rs9939609, and HHEX rs1111875 and rs5015480 were all genotyped using the SNPscan™ genotyping assay. The independent sample t-test, logistic regression, and chi-square test were used to assess the variations in genotype and allele and their relationships with the risk of GDM. The blood glucose level, gestational week of delivery, and newborn weight were compared using a one-way ANOVA.ResultsAfter adjusting for confounding factors, the results show that the rs1111875 heterozygous (OR=1.370; 95% CI: 1.040-1.805; P = 0.025) and overdominant (OR=1.373; 95% CI: 1.049-1.796; P = 0. 021) models are significantly associated with an increased risk of GDM, especially for the age ≥ 30 years group: heterozygote (OR=1.646; 95% CI: 1.118-2.423; P=0.012) and overdominant (OR=1.553; 95% CI: 1.064-2.266; P = 0.022) models. In the age ≥ 30 years, the rs5015480 overdominant model (OR=1.595; 95% CI: 1.034-2.459; P = 0.035) and the rs9939609 heterozygote model (OR=1.609; 95% CI: 1.016-2.550; P=0.043), allele (OR=1. 504; 95% CI: 1.006-2.248; P = 0.047), dominant model (OR=1.604; 95% CI: 1.026-2.505; P = 0.038), and overdominant model (OR=1.593; 95% CI: 1.007-2.520; P = 0.047) were associated with a significantly increased risk of GDM; Additionally, people with the TC genotype of rs1111875 had a substantially higher 1-hour blood glucose level than TT genotype (P < 0.05). The results of the meta-analysis showed that the A allele of rs11705701 was associated with an increased risk of diabetes mellitus (P < 0.05).ConclusionThe study indicates that the TC genotype of rs1111875 is linked to a higher risk of GDM, particularly in women aged 30 years or older. Additionally, rs5015480 and rs9939609 were significantly associated with GDM in the same age group. These SNPs may therefore be more closely linked to GDM in older mothers.
| S-EPMC11628248 | biostudies-literature
Project description: Not available
| S-EPMC4075489 | biostudies-literature
Project description:ObjectivesThis case-control study aims to clarify the impact of single nucleotide polymorphisms (SNPs) within the P2X7 gene on susceptibility to type 2 diabetes mellitus (T2DM) and to evaluate their association with diabetic complications.MethodsThis study is comprised with 200 T2DM cases and 200 healthy controls. Seven candidate SNP loci were screened, and TaqMan-MGB real-time PCR technology was used to determine the polymorphic variants of P2X7. Different genotype and allele frequencies were compared by Pearson's χ2 tests and logistic regression analysis.ResultsThree P2X7 SNPs were found to be associated with T2DM risk. Specifically, rs7958311 GA (OR = 1.323, p = 0.002), rs7958311 AA (OR = 1.508, p = 0.038), rs208294 CC (OR = 1.854, p = 0.042) showed a higher susceptibility to T2DM, whilst rs11065464 CA (OR = 0.614, p = 0.022) was associated with a reduced risk. Logistic regression analysis indicated that rs7958311 was linked to an increased risk for nephropathy (OR = 1.833, p = 0.022), but with a decreased risk for peripheral artery disease (OR = 0.550, p = 0.042). Additionally, rs208294 was identified as a risk factor for peripheral neuropathy (OR = 2.101, p = 0.016).ConclusionsWe found that P2X7 polymorphisms are significantly associated with the risk of T2DM and its complications, suggesting that targeting P2X7 may offer a novel therapeutic strategy for the prevention and personal treatment of T2DM.
| S-EPMC11771865 | biostudies-literature
Project description:Many studies have examined the associations between paraoxonase-1 (PON1) genetic polymorphisms (Q192R, rs662 and L55M, rs854560) and the susceptibility to type 2 diabetes mellitus (T2DM) across different ethnic populations. However, the evidence for the associations remains inconclusive. In this study, we performed a meta-analysis to clarify the association of the two PON1 variants with T2DM risk. We carried out a systematic search of PubMed, Embase, CNKI and Wanfang databases for studies published before June 2017. The pooled odds ratios (ORs) for the association and their corresponding 95% confidence intervals (CIs) were calculated by a random- or fixed-effect model. A total of 50 eligible studies, including 34 and 16 studies were identified for the PON1 Q192R (rs662) and L55M (rs854560) polymorphism, respectively. As for the PON1 Q192R polymorphism, the 192R allele was a susceptible factor of T2DM in the South or East Asian population (OR > 1, P < 0.05) but represented a protective factor of T2DM in European population (OR = 0.66, 95% CI = 0.45-0.98) under a heterozygous genetic model. With regard to the PON1 L55M polymorphism, significant protective effects of the 55M allele on T2DM under the heterozygous (OR = 0.77, 95% CI = 0.61-0.97) and dominant (OR = 0.80, 95% CI = 0.65-0.99) genetic models were found in the European population, while no significant associations in the Asian populations under all genetic models (P > 0.05). In summary, by a comprehensive meta-analysis, our results firmly indicated that distinct effects of PON1 genetic polymorphisms existed in the risk of T2DM across different ethnic backgrounds.
| S-EPMC5824408 | biostudies-literature
Project description:Type 1 diabetes (T1D) and celiac disease (CeD) cluster in families and can occur in the same individual. Genetic loci have been associated with susceptibility to both diseases. Our aim was to explore the genetic differences between individuals developing both these diseases (double autoimmunity) versus those with only one. We hypothesized that double autoimmunity individuals carry more of the genetic risk markers that are shared between the two diseases independently. SNPs were genotyped in loci associated with T1D (n=42) and CeD (n=28) in 543 subjects who developed double autoimmunity, 2,472 subjects with T1D only, and 2,223 CeD-only subjects. For identification of loci that were specifically associated with individuals developing double autoimmunity, two association analyses were conducted: double autoimmunity versus T1D and double autoimmunity versus CeD. HLA risk haplotypes were compared between the two groups. The CTLA4 and IL2RA loci were more strongly associated with double autoimmunity than with either T1D or CeD alone. HLA analyses indicated that the T1D high-risk genotype, DQ2.5/DQ8, provided the highest risk for developing double autoimmunity (odds ratio 5.22, P=2.25×10(-29)). We identified a strong HLA risk genotype (DQ2.5/DQ8) predisposing to double autoimmunity, suggesting a dominant role for HLA. Non-HLA loci, CTLA4 and IL2RA, may also confer risk to double autoimmunity. Thus, CeD patients who carry the DQ2.5/DQ8 genotype may benefit from periodic screening of autoantibodies related to T1D.
| S-EPMC4582914 | biostudies-literature
Project description:BackgroundTwo inflammatory disorders, type 1 diabetes and celiac disease, cosegregate in populations, suggesting a common genetic origin. Since both diseases are associated with the HLA class II genes on chromosome 6p21, we tested whether non-HLA loci are shared.MethodsWe evaluated the association between type 1 diabetes and eight loci related to the risk of celiac disease by genotyping and statistical analyses of DNA samples from 8064 patients with type 1 diabetes, 9339 control subjects, and 2828 families providing 3064 parent-child trios (consisting of an affected child and both biologic parents). We also investigated 18 loci associated with type 1 diabetes in 2560 patients with celiac disease and 9339 control subjects.ResultsThree celiac disease loci--RGS1 on chromosome 1q31, IL18RAP on chromosome 2q12, and TAGAP on chromosome 6q25--were associated with type 1 diabetes (P<1.00x10(-4)). The 32-bp insertion-deletion variant on chromosome 3p21 was newly identified as a type 1 diabetes locus (P=1.81x10(-8)) and was also associated with celiac disease, along with PTPN2 on chromosome 18p11 and CTLA4 on chromosome 2q33, bringing the total number of loci with evidence of a shared association to seven, including SH2B3 on chromosome 12q24. The effects of the IL18RAP and TAGAP alleles confer protection in type 1 diabetes and susceptibility in celiac disease. Loci with distinct effects in the two diseases included INS on chromosome 11p15, IL2RA on chromosome 10p15, and PTPN22 on chromosome 1p13 in type 1 diabetes and IL12A on 3q25 and LPP on 3q28 in celiac disease.ConclusionsA genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles. These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases.
| S-EPMC2840835 | biostudies-literature
Project description:Various mutations in microRNAs (miRs) are associated with the pathogenesis of several diseases including cancers and vascular diseases. The present study aimed to investigate the potential association between miR-27a A>G (rs895819) and miR-449b A>G (rs10061133) polymorphisms with the prevalence of type 2 diabetes mellitus (T2DM), and its associated risk factors in the Korean population. Genotype analysis was performed using PCR-restriction fragment length polymorphism analysis to assess the frequency of miR-27a and miR-449b gene polymorphisms in patients diagnosed with T2DM (n=238) and healthy controls (n=247). The miR-27a GG genotype, recessive model, and G allele were significantly associated with a decreased risk of T2DM [adjusted odds ratio (AOR)=0.378, 95% confidence interval (CI): 0.208-0.686, P=0.001; AOR=0.425, 95% CI: 0.246-0.734, P=0.002; AOR=0.640, 95% CI: 0.493-0.831, P=0.001, respectively). Although the miR-449b polymorphism was not associated with the prevalence of T2DM, the genotype and allele combination analyses for miR-27a and miR-449b polymorphisms showed associations with T2DM prevalence. Furthermore, stratification analysis revealed that the miR-27a polymorphism was associated with DM risk factors including body mass index (<28.12 kg/m2, P=0.031), waist circumference (<93.03 cm, P=0.036), systolic blood pressure (<132.67 mmHg, P=0.017), fasting blood glucose levels (<106.26 mg/dl, P=0.015), glycosylated hemoglobin, type A1C (≤125.5 mg/dl, P=0.001), total cholesterol (≤240 mg/dl, P=0.010) and low-density lipoprotein levels (≤130 mg/dl, P=0.028). The present study revealed an association between miR-27a A>G and miR-449b A>G polymorphisms and the risk of DM in Koreans, which suggests that these gene polymorphisms could represent potential markers for predicting T2DM risk.
| S-EPMC8972843 | biostudies-literature
Project description:The present study aimed to investigate the roles of insulin related gene IGF2BP2, HMG20A, and HNF1B variants in the susceptibility of Type 2 diabetes mellitus (T2DM), and to identify their association with age, gender, BMI, and smoking and alcohol drinking behavior among the Han Chinese population. About 508 patients with T2DM and 503 healthy controls were enrolled. Rs11927381 and rs7640539 in IGF2BP2, rs7178572 in HMG20A, rs4430796, and rs11651052 in HNF1B were genotyped by using the Agena MassARRAY. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression. We found that HMG20A rs7178572 (OR = 1.25, P = 0.015) and HNF1B rs11651052 (OR = 1.26, P = 0.019) increased the risk of T2DM. Rs7178572, rs4430796, and rs11651052 might be related to the higher T2DM susceptibility not only by itself but also by interacting with age, gender smoking, and alcohol drinking. Rs11927381 also conferred the higher T2DM susceptibility at age ≤ 59 years. Besides, rs7178572-AA (P = 0.032) genotype and rs11651052 GG (P = 0.018) genotype were related to higher glycated hemoglobin and insulin level, respectively. Specifically, we first found that rs11927381, rs7640539, and rs11651052 were associated with risk of T2DM among the Han Chinese population. We also provide evidence that age, gender, BMI, smoking, and drinking status have an interactive effect with these variants on T2DM susceptibility.
| S-EPMC7256674 | biostudies-literature