Vitamin D gene polymorphisms are associated with type 1 diabetes mellitus in Korean youth
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SUBMITTER: Nam H
PROVIDER: S-EPMC3850115 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundType 1 diabetes mellitus (TIDM) results from an immune-mediated destruction of insulin-producing-cells in the pancreatic islets of Langerhans. There are clear differences in immunogenetic predisposition to type1 diabetes among countries. Studies have indicated that vitamin D supplementation in early childhood decreases the risk of TIDM. Vitamin D exerts its action via the nuclear vitamin D receptor (VDR), which shows an extensive polymorphism. VDR gene polymorphisms have been associated with altered gene expression or gene function. Four single nucleotide polymorphisms (SNPs) in the VDR gene produce variation in four recognition sites. These recognition sites variants include Fok I, Bsm I, Apa I and Taq I.Aim of the studyTO investigate the relationship between VDR gene polymorphisms (at positions Taq I and Apa I) and the incidence of TIDM in Egyptian peoples.Subjects and methodsThis study included 74 patients with type 1 DM in addition to 28 healthy age and sex matched control subjects. All of them were subjected to full history taking and clinical examination. Three ml of venous blood were withdrawn from each patient at fasting and postprandial times and used for genomic DNA extraction, estimation of Hb A1C, as well as, fasting and postprandial C-peptide and blood glucose levels.ResultsApa I recognition site was found in low frequency in diabetic patients (14/74) 18.9% while, its frequency was high (16/28) 57.1% among normal subjects. Taq I has two recognition sites. The first was found at nucleotide number 293 that was found in a frequency of (2/28) 7.1% in normal non-diabetic individuals while it was detected in (14/74) 18.9% in diabetic patients. The second Taq I recognition site was found at nucleotide number 494 without any differences between diabetic and normal individuals.ConclusionThis study indicates that there is an association between VDR genetic polymorphism and incidence of TIDM in Egyptian patients.
| S-EPMC4307509 | biostudies-literature
Project description:BackgroundVitamin D receptor (VDR) polymorphisms are associated with osteoporosis, diabetes, immunological diseases, and cancers. However, the association of obesity with VDR polymorphisms has shown inconsistent results, and perhaps it depends upon the characteristics of a population. Therefore, we evaluated the association between BsmI (rs1544410) and ApaI (rs7975232) polymorphisms of VDR and obesity in Korean patients with type 2 diabetes mellitus (T2DM).MethodsA total of 506 patients with T2DM participated in the study. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze BsmI and ApaI polymorphisms; the genotypes were presented as BB, Bb, or bb for BsmI and AA, Aa, or aa for ApaI. Obesity was defined using the body mass index (BMI) with a cutoff level of 25 kg/m2.ResultsThe prevalence of obesity was higher in patients with the bb genotype than in those with BB or Bb genotypes (48.4% vs 33.9%, P = 0.031). The mean BMI was 25.2 ± 3.5 kg/m2 in patients with bb genotype and 24.1 ± 3.1 kg/m2 in patients with BB or Bb genotypes. Patients with Aa or aa genotypes showed a higher prevalence of obesity than patients with AA genotype (47.6% vs 26.1%, P = 0.043). Glycemic control parameters and lipid profiles did not show significant differences with either polymorphism.ConclusionTo our knowledge, this is the first study to assess the association between VDR polymorphisms and obesity in Korean patients with T2DM. Further studies in larger populations and multiethnic cohorts are needed to validate our findings.
| S-EPMC7882455 | biostudies-literature
Project description:BackgroundThe incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore, VDR gene may be considered a candidate for T1DM susceptibility.MethodsThe genotypes of four VDR gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays.ResultsStatistically significant differences were detected between the genotypes of two VDR gene polymorphisms (FokI, C > T, rs10735810 and TaqI, C > T, rs731236) between T1DM patients and controls (P < 0.0001). In both, the frequency of variant alleles was considerably high in T1DM than in the controls. In contrast, the VDR gene ApaI (G > T, rs7975232) and BsmI (A > G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of FokI, ApaI and TaqI polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of BsmI polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and > 6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different VDR gene polymorphism genotypes.ConclusionsOur results demonstrate a significant effect of two VDR gene polymorphisms (FokI and TaqI) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.
| S-EPMC6404350 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) is a leading cause of death. The prevalence of T2DM in countries of the Middle East and North Africa (MENA) region, including Jordan, is among the highest worldwide. The reason(s) behind the epidemic nature of T2DM in Jordan are unknown but warrant further exploration. Studies have indicated that T2DM could be influenced by diet and/or genetic background. Evidence suggests that numerous patients with T2DM are deficient in vitamin D. The activity of vitamin D on its target tissues may be influenced by single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene. It was therefore hypothesized that SNPs in VDR could modify the risk of T2DM. To test this hypothesis, 125 patients with T2DM were recruited along with 125 controls. The study subjects were genotyped for variations in rs2228570, rs1544410, rs7975232, and rs731236 SNPs in the VDR. The levels of 25-hydroxyvitamin D [25(OH)D] were measured from the serum. The analysis revealed that reduced 25(OH)D and age were associated with the risk of T2DM (P<0.05). Moreover, under a dominant inheritance model, the GG genotype of rs2228570 was revealed to increase the risk of T2DM in univariate and multivariate analysis (P<0.05). Additionally, a chromosomal block containing the GAAG haplotype of VDR SNPs increased the risk of T2DM (OR=1.909; CI: 1.260-2.891; P=0.0021). Collectively, the present study revealed that low levels of serum 25(OH)D and rs2228570 of the VDR gene are associated with the risk of T2DM.
| S-EPMC9755923 | biostudies-literature
Project description:Diabetes is currently a growing concern of the age. Prevention and treatment of diabetes is a global health priority. Adiponectin is an adipocyte derived protein hormone that enhances insulin sensitivity and ameliorates diabetes by enhancing fatty acid oxidation and glucose uptake in skeletal muscle and reducing glucose production in the liver. Low serum adiponectin concentrations are associated with diabetes, central obesity, insulin resistance and metabolic syndrome. Adiponectin gene is located on chromosome 3q27, where a locus of susceptibility to diabetes was mapped. Several cross-sectional studies showed that single nucleotide polymorphisms (SNPs) in adiponectin gene (ADIPOQ) were associated with diabetes. SNPs in ADIPOQ help in assessing the association of common variants with levels of adiponectin and the risk of diabetes. Two common SNPs, rs2241766 and rs1501299, have been linked significantly to type 1 diabetes mellitus which endow the world with a block of haplotypes. Experimental evidences also suggest that rs1501299, rs2241766, rs266729, rs17366743, rs17300539, rs182052, rs822396, rs17846866, rs3774261 and rs822393 are significantly associated with type 2 diabetes mellitus which is the predominant form of the disease. In addition, rs2241766 and rs266729 are extensively associated with gestational diabetes, a condition that develops in women during pregnancy. Therefore not a particular single mutation but a number of SNPs in adiponectin gene could be a risk factor for developing diabetes among the individuals worldwide. This study firmly suggests that adiponectin plays a crucial role in the pathogenesis of type 1, type 2 and gestational diabetes mellitus.
| S-EPMC8387910 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM), by definition is a heterogeneous, multifactorial, polygenic syndrome which results from insulin receptor (IR) dysfunction. It is an outcome of oxidative stress caused by interactions of reactive metabolites (RMs) with lipids, proteins and other molecules of the human body. Production of RMs mainly superoxides (•O2 (-)) has been found in a variety of predominating cellular enzyme systems including nicotinamide adenine dinucleotide phosphate oxidase, xanthine oxidase, cyclooxygenase, endothelial nitric oxide synthase (eNOS) and myeloperoxidase. The four main RM related molecular mechanisms are: increased polyol pathway flux; increased advanced glycation end-product formation; activation of protein kinase C isoforms and increased hexosamine pathway flux which have been implicated in glucose-mediated vascular damage. Superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and NOS are antioxidant enzymes involved in scavenging RMs in normal individuals. Functional polymorphisms of these antioxidant enzymes have been reported to be involved in the pathogenesis of T2DM. The low levels of antioxidant enzymes or their non-functionality results in excessive RMs which initiates stress related pathways thereby leading to IR and T2DM. An attempt has been made to review the role of RMs and antioxidant enzymes in oxidative stress resulting in T2DM.
| S-EPMC4065473 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM), by definition is a heterogeneous, multifactorial, polygenic syndrome which results from insulin receptor dysfunction. It is an outcome of oxidative stress caused by interactions of reactive metabolites (RMs) interactions with lipids, proteins and other mechanisms of human body. Production of RMs mainly superoxide (O2(-)) has been found in a variety of predominating cellular enzyme systems including NAD(P)H oxidase, xanthine oxidase (XO), cyclooxygenase (COX), uncoupled endothelial nitric oxide synthase (eNOS) and myeloperoxidase (MPO). The four main RM related molecular mechanisms are: increased polyol pathway flux; increased advanced glycation end-product (AGE) formation; activation of protein kinase C (PKC) isoforms and increased hexosamine pathway flux which have been implicated in glucose-mediated vascular damage. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), nitric oxide synthase (NOS) are antioxidant enzymes involved in scavenging RMs in normal individuals. Functional polymorphisms of these antioxidant enzymes have been reported to be involved in pathogenesis of T2DM individuals. The low levels of antioxidant enzymes or their non-functionality results in excessive RMs which initiate stress related pathways thereby leading to insulin resistance and T2DM. An attempt has been made to review the role of RMs and antioxidant enzymes in oxidative stress resulting in T2DM.
| S-EPMC4297945 | biostudies-literature
Project description:Genetic variations in calpain-10 and adiponectin gene are known to influence insulin secretion and resistance in type 2 diabetes mellitus. Recently, several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene have been reported to be associated with type 2 diabetes and various metabolic derangements. We investigated the associations between specific calpain-10 and adiponectin gene polymorphisms and Korean type 2 diabetes patients.Overall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The clinical characteristics and measure of glucose metabolism were compared within these genotypes.Among calpain-10 polymorphisms, SNP-63 T/T were more frequent in diabetes patients, and single SNP-63 increases the susceptibility to type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in adiponectin gene were not significantly associated with diabetes, insulin resistance, nor insulin secretion.Variations in calpain-10, SNP-63 seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43 and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism.
| S-EPMC6145956 | biostudies-literature
Project description:ObjectivesAQP7 and AQP9 represent glycerol channel in adipose tissue and liver and have been associated with metabolic diseases. We aimed to investigate the associations between genetic variants in AQP7 and AQP9 genes and the risk of type 2 diabetes (T2DM) in Chinese population.MethodsBlood samples were drawn from 400 T2DM patients and 400 age- and gender-matched controls. Genomic DNA was extracted by proteinase K digestion and phenol-chloroform extraction. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs62542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes.ResultsThe subjects with rs2989924 GA+AA genotypes had 1.47-fold increased risk of T2DM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.06-2.04), compared to those with GG genotype, and this association remained significant after adjustment for covariates (OR 1.66, 95% CI 1.07-2.57). When compared with rs3758269 CC genotype, the subjects with CT+TT genotypes had 45% decreased T2DM risk after multivariate adjustment (OR 0.55, 95% CI 0.35-0.85). The associations were evident in elder and overweight subjects and those with central obesity. No association was observed between AQP9 SNPs and T2DM risk.ConclusionsAQP7 SNP rs2989924 and rs3758269 were associated with T2DM risk in Chinese Han population.
| S-EPMC6288565 | biostudies-literature
Project description:AimsTo investigate the association between Vitamin D receptor gene polymorphisms (BsmI, TaqI and FokI) and type 2 diabetes mellitus in patients in north eastern India.Settings and designThis was a case control study with 40 cases of type 2 diabetes and 20 controls.Materials and methodsGenomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNPs) of BsmI [rs1544410], TaqI [rs731236] and FokI [rs2228570] by polymerase chain reaction and gene sequencing. Genotype distribution and allelic frequencies were compared between patients and controls. Data was expressed as mean ±standard deviation. Chi square test and t test were used to compare groups. Statistical analysis was done using SAS version 9.3 software. P value of <0.05 was considered significant.ResultsBody weight and BMI were significantly associated with VDR polymorphisms BsmI and TaqI while BsmI was significantly associated with HbA1C. Vitamin D deficiency was significantly greater in cases than controls. The frequency of the heterozygous genotype of the BsmI polymorphism was significantly greater in type 2 diabetics than in controls.ConclusionsVitamin D receptor polymorphisms are associated with type 2 diabetes in our population and require larger scale studies to be considered as possible risk factors or type 2 diabetes mellitus.
| S-EPMC5972480 | biostudies-literature