Dataset Information

Association of JAZF1 and TSPAN8/LGR5 variants in relation to type 2 diabetes mellitus in a Saudi population.

ABSTRACT: BACKGROUND:Type 2 diabetes mellitus (T2DM) is a chronic and multifactorial disease with a rapidly rising incidence in Saudi Arabia. Various genes including zinc finger protein 1 (JAZF1) and tetraspanin 8/leucine-rich repeat-containing G protein-coupled receptor (TSPAN8/LGR5) have been previously described to be associated with T2DM. This study investigated the association of JAZF1 (rs864745) and TSPAN8 (rs7961581) with T2DM in a Saudi population. METHODS:Genomic DNA samples from 400 Saudi T2DM patients and 400 healthy controls were genotyped and analyzed using a polymerase chain reaction-restriction fragment length polymorphism method. The difference between the genotype frequencies were carried out with Chi-square test. Odds ratio, 95 % confidence intervals and p values were calculated using multinomial logistic regression. Dominant and recessive models were implemented to show the statistical significances. Analysis of variance was used to compare differences between genotypes for the various parameters. RESULTS:Distribution frequencies of the AA, AG, and GG genotypes of JAZF1 (rs864745) differed significantly among T2DM patients and healthy controls (p < 0.05). The AG and GG genotypes were independently and significantly associated with a T2DM risk after adjusting for factors such as age, sex, and body mass index [odds ratio (OR) 2.1 (95 % confidence interval (CI) 1.3-3.4); p = 0.002] and [OR 1.9 (95 % CI 1.2-3.1); p = 0.005], respectively. A genotype-based stratification of anthropometric and biochemical data revealed that the AG + GG genotype is associated with waist circumference (p = 0.04) and fasting blood glucose (p = 0.01) and high-density lipoprotein cholesterol levels (p = 0.02). None of the allele or genotype showed the significant association between the T2DM cases and control subjects in rs7961581 polymorphism in TSPAN8/LGR5 gene. CONCLUSION:The rs864745 variant in JAZF1 gene may act as genetic risk factors for the development of T2DM in a Saudi population.

SUBMITTER: Alharbi KK

PROVIDER: S-EPMC4619989 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association of JAZF1 and TSPAN8/LGR5 variants in relation to type 2 diabetes mellitus in a Saudi population.

Alharbi Khalid Khalaf KK Ali Khan Imran I Syed Rabbani R Alharbi Fawiziah Khalaf FK Mohammed Abdul Khader AK Vinodson Benjamin B Al-Daghri Nasser M NM

Diabetology & metabolic syndrome 20151024

<h4>Background</h4>Type 2 diabetes mellitus (T2DM) is a chronic and multifactorial disease with a rapidly rising incidence in Saudi Arabia. Various genes including zinc finger protein 1 (JAZF1) and tetraspanin 8/leucine-rich repeat-containing G protein-coupled receptor (TSPAN8/LGR5) have been previously described to be associated with T2DM. This study investigated the association of JAZF1 (rs864745) and TSPAN8 (rs7961581) with T2DM in a Saudi population.<h4>Methods</h4>Genomic DNA samples from 4 ...[more]

PMID: 26500707

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Project description:BackgroundGlyoxalase 1 (GLO1) plays a crucial role in defending against glycation. Single nucleotide polymorphism (SNP) variants in the GLO1 gene may affect gene expression and alter enzyme activity. However, there have been limited studies evaluating the association between GLO1 and diabetes, especially gestational diabetes mellitus (GDM). Therefore, this study is the first to explore the association of GLO1 SNPs and GDM risk.MethodsThe study included a total of 500 GDM patients and 502 control subjects. The SNPscan™ genotyping assay was used to genotype rs1781735, rs4746 and rs1130534. To assess the disparities in genotype, allele, and haplotype distributions and their correlation with GDM risk, the independent sample t-test, logistic regression, and chi-square test were employed during the data processing phase. Furthermore, one-way ANOVA was conducted to determine the differences in genotype and blood glucose and methylglyoxal(MG) levels.ResultsSignificant differences were observed in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP), and parity between GDM and healthy subjects (P < 0.05). After adjusting for these factors, GLO1 rs1130534 TA remained associated with an increased risk of GDM (TA vs. TT + AA: OR = 1.320; 95% CI: 1.008-1.728; P = 0.044), especially in the pre-BMI ≥ 24 subgroup (TA vs. TT + AA: OR = 2.424; 95% CI: 1.048-5.607; P = 0.039), with fasting glucose levels being significantly elevated in the TA genotype compared to the TT genotype (P < 0.05). Conversely, the GLO1 rs4746 TG was associated with a decreased risk of GDM (TG vs. TT: OR = 0.740; 95% CI: 0.548-0.999; P = 0.049; TG vs. TT + GG: OR = 0.740; 95% CI: 0.548-0.998; P = 0.048). Additionally, the haplotype T-G-T of rs1781735, rs4746 and rs1130534 was associated with a decreased risk of GDM among individuals with a pre-BMI ≥ 24 (OR = 0.423; 95% CI: 0.188-0.955; P = 0.038). Furthermore, the rs1781735 GG genotype was found to be more closely related to maternal MG accumulation and neonatal weight gain (P < 0.05).ConclusionOur findings suggested that GLO1 rs1130534 was associated with an increased susceptibility to GDM and higher blood glucose levels, but GLO1 rs4746 was associated with a decreased risk of GDM. The rs1781735 has been associated with the accumulation of maternal MG and subsequent weight gain in neonates.

Project description:ObjectiveTo explore the relationship between angiotensin-converting enzyme 2 (ACE2) genetic variants and gestational diabetes mellitus (GDM) in a southern Chinese population.MethodsPotential functional variants (rs2106809, rs6632677, and rs2074192) of ACE2 were selected and genotyped in 566 GDM patients and 710 normal pregnaõncies in Guilin, China. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were used to evaluate the association between genetic variant and GDM risk, and then the false positive report probability, multifactor dimensional reduction (MDR), and bioinformatics tools were used to confirm the significant association in the study.ResultsAfter adjusting for age and prepregnancy body mass index, logistic regression analysis showed that ACE2 rs6632677 was significantly associated with a decreased risk of GDM (CC vs. GG: adjusted OR = 0.09, 95% CI: 0.01 - 0.71, P = .023; GC/CC vs. GG: adjusted OR = 0.68, 95% CI = 0.46 - 0.99, P = .048; and CC vs. GG/GC: adjusted OR = 0.09, 95% CI = 0.01 - 0.72, P = .024), whereas rs2074192 was associated with increased GDM risk (TT vs. CC/CT: adjusted OR = 1.38, 95% CI = 1.08 - 1.75, P = .009). Furthermore, we found that rs6632677 interacted with SBP (P interaction = .043) and FPG (P interaction = .021) and rs2074192 interacted with HDL-c (P interaction = .029) and LDL-c (P interaction = .035) to influence the GDM risk of the individual. In the MDR analysis, the rs6632677 was the best one-locus model, and the three-loci model was the best interaction model to predict GDM risk. In addition, functional analysis confirmed that rs2074192 may regulate the splicing process of ACE2 gene.ConclusionACE2 gene variants are significantly associated with the risk of GDM via gene-gene and gene-environment combinations. The rs2074192 C > T affects the splicing of the ACE2 gene, which may be a potential mechanism leading to the changed susceptibility of an individual female during pregnancy to GDM.

Dataset Information

Association of JAZF1 and TSPAN8/LGR5 variants in relation to type 2 diabetes mellitus in a Saudi population.

Publications

Association of JAZF1 and TSPAN8/LGR5 variants in relation to type 2 diabetes mellitus in a Saudi population.

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