Type 2 Diabetes Mellitus Susceptibility Research Articles

Causal relationship between type 1 diabetes mellitus and six high-frequency infectious diseases: A two-sample mendelian randomization study.

Type 1 diabetes mellitus (T1DM) is associated with different types of infections; however, studies on the causal relationship between T1DM and infectious diseases are lacking. Therefore, our study aimed to explore the causalities between T1DM and six high-frequency infections using a Mendelian randomization (MR) approach. Two-sample MR studies were conducted to explore the causalities between T1DM and six high-frequency infections: sepsis, acute lower respiratory infections (ALRIs), intestinal infections (IIs), infections of the genitourinary tract (GUTIs) in pregnancy, infections of the skin and subcutaneous tissues (SSTIs), and urinary tract infections (UTIs). Data on summary statistics for T1DM and infections were obtained from the European Bioinformatics Institute database, the United Kingdom Biobank, FinnGen biobank, and Medical Research Council Integrative Epidemiology Unit. All data obtained for summary statistics were from European countries. The inverse-variance weighted (IVW) method was employed as the main analysis. Considering the multiple comparisons, statistical significance was set at p< 0.008. If univariate MR analyses found a significant causal association, multivariable MR (MVMR) analyses were performed to adjust body mass index (BMI) and glycated hemoglobin (HbA1c). MVMR-IVW was performed as the primary analysis, and the least absolute shrinkage and selection operator (LASSO) regression and MVMR-Robust were performed as complementary analyses. MR analysis showed that susceptibility to IIs increased in patients with T1DM by 6.09% using the IVW-fixed method [odds ratio (OR)=1.0609; 95% confidence interval (CI): 1.0281-1.0947, p=0.0002]. Results were still significant after multiple testing. Sensitivity analyses did not show any significant horizontal pleiotropy or heterogeneity. After adjusting for BMI and HbA1c, MVMR-IVW (OR=1.0942; 95% CI: 1.0666-1.1224, p<0.0001) showed significant outcomes that were consistent with those of LASSO regression and MVMR-Robust. However, no significant causal relationship was found between T1DM and sepsis susceptibility, ALRI susceptibility, GUTI susceptibility in pregnancy, SSTI susceptibility, and UTI susceptibility. Our MR analysis genetically predicted increased susceptibility to IIs in T1DM. However, no causality between T1DM and sepsis, ALRIs, GUTIs in pregnancy, SSTIs, or UTIs was found. Larger epidemiological and metagenomic studies are required to further investigate the observed associations between the susceptibility of certain infectious diseases with T1DM.

Genetic Risk Scores for the Determination of Type 2 Diabetes Mellitus (T2DM) in North India

Globally, type 2 diabetes mellitus (T2DM) is one of the fastest-growing noncommunicable multifactorial and polygenic diseases, which leads to many health complications and significant morbidity and mortality. South Asians have a high genetic predisposition to T2DM, with India being home to one in six diabetics. This study investigates the association of selected genetic polymorphisms with T2DM risk and develops a polygenic risk score (PRS). A case-control study recruited fully consented participants from a population of Jat Sikhs in north India. DNA samples were genotyped for a range of polymorphisms and odds ratios were calculated under several genetic association models. Receiver operating characteristic (ROC) curves were produced for combinations of the PRS and clinical parameters. The GSTT1(rs17856199), GSTM1(rs366631), GSTP1(rs1695), KCNQ1(rs2237892), ACE(rs4646994), and TCF7L2(rs12255372; rs7903146; rs7901695) polymorphisms were associated with increased T2DM risk (p ≤ 0.05). No association was observed with IGF2BP2(rs4402960) or PPARG2(rs1801282). The weighted PRS was found to be significantly higher in patients (mean = 15.4, SD = 3.24) than controls (mean = 11.9, SD = 3.06), and t(454) = -12.2 (p < 0.001). The ROC curve analysis found the weighted PRS in combination with clinical variables to be the most effective predictor of T2DM (area under the curve = 0.844, 95%CI = 0.0.808-0.879). Several polymorphisms were associated with T2DM risk. PRS based on even a limited number of loci improves the prediction of the disease. This may provide a useful method for determining T2DM susceptibility for clinical and public health applications.

Association of TCF7L2 Gene Variant (rs12255372) with Polycystic Ovary Syndrome and its Effect Modification of the Disease Phenotype.

Polycystic ovary syndrome (PCOS) and type-2 diabetes mellitus (T2DM) share common genetic features. Transcription factor 7-like-2 (TCF7L2) is consistently studied T2DM susceptibility locus. However, limited studies on TCF7L2 have failed to demonstrate any link with the PCOS risk. Therefore, we investigated the association of TCF7L2 polymorphic variant (rs12255372) with the PCOS risk. We recruited 120 PCOS cases, diagnosed as per Rotterdam 2003 criteria, and an equal number of age-matched controls. Besides a detailed clinical assessment, subjects underwent biochemical and hormonal profiling. Genotyping for rs12255372 was done by PCR-RFLP. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of genotype-phenotype correlations. The PCOS cases reported fewer menstrual cycles per year and exhibited signs of hyperandrogenism. The heterozygous genotype of rs12255372 was strongly associated with the PCOS risk (OR = 2.00; 95%CI: 1.07-3.76). Unlike controls, only 3 cases harbored TT genotype, and the PCOS risk persisted in the dominant model (GT + TT) as well. Moreover, we found a synergistic effect modification by the variant genotype in the subjects who had family histories of T2DM, hirsutism, or menstrual irregularities. We report a significant association of the TCF7L2 polymorphic variant rs12255372 with the PCOS risk.

Association between the RETN -420C/G polymorphism and type 2 diabetes mellitus susceptibility: A meta-analysis of 23 studies.

The published findings on the link between the resistin (RETN) gene polymorphism and type 2 diabetes mellitus (T2DM) risk are still contradictory. Here, through a meta-analysis, we summarized a more precise evaluation of their connection by synthesizing existing research. PubMed, Google Scholar, and Web of Science were electronically searched, and all cited sources were manually searched. The heterogeneity of effects was tested and all statistical analyses were performed in Stata 12.0. A total of 23 studies with 10,651 cases and 14,366 controls on RETN -420C/G polymorphism were included. The overall results showed that the association of RETN -420C/G polymorphism and T2DM susceptibility was not significant [for the allelic model: odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.87-1.10, pheterogeneity <.001; I 2 = 84.6%; for the dominant model: OR = 0.96, 95% CI = 0.80-1.15, pheterogeneity <.001; I 2 = 87.1%; and for the recessive model: OR = 0.96, 95% CI = 0.82-1.12, pheterogeneity <.001; I 2 = 56.9%] but with high heterogeneity across studies (p <.0001). Meta-regression found that the median age of T2DM participants (using age 50 as the cutoff) could be a factor in the observed variation. The RETN -420C/G polymorphism seems to be linked to an increased risk of T2DM in younger individuals [for dominant: OR = 0.84 (95% CI, 0.72-0.98; pheterogeneity <.001; I 2 = 80.9%)] and decreased risk in older people [for dominant: OR = 3.14 (95% CI, 2.35-4.19; pheterogeneity = .98; I 2 = 0.0%)]. Current results found no evidence that the RETN -420C/G variant was linked to T2DM susceptibility, but the patient's age appears to be a potential factor that contributed to high heterogeneity across studies. Additional high-quality and well-designed investigations are required to confirm these results.

Association of cumulative monocyte to high-density lipoprotein ratio with the risk of type 2 diabetes: a prospective cohort study

BackgroundRecent studies have established that monocyte-derived inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM). It is unclear whether chronic metabolic inflammation, reflected by the cumulative monocyte to high-density lipoprotein ratio (CumMHR), predisposes the general population to T2DM.MethodsThis study included 40,813 participants without diabetes from a real-life, community-based cohort (the Kailuan Study) attending a 2-year cycle of health survey since 2006. Cumulative exposure was obtained from 2006/2007 to 2010/2011. Follow-up started at 2010/2011 and through 2020. Multivariable-adjusted Cox regression models were used to calculate the CumMHR-associated risk of incident T2DM.ResultsOver a median follow-up period of 7.98 (IQR: 5.74–8.87) years, 4,848 T2DM cases occurred. The CumMHR was positively associated with the risk of incident T2DM after adjusting for age, sex, smoking, drinking habits, physical activities, BMI, triglyceride-glycemia index, log(leukocyte count), log(hsCRP), blood pressure, renal function, and medication uses with adjusted HRs of 1.0 (ref.), 1.18 (1.05‒1.25), 1.17 (1.07‒1.27), 1.38 (1.26‒1.50), respectively, in CumMHR Quartiles 1, 2, 3 and 4. When follow-up ended at 2014/2015, the short-term (4‒year) adjusted T2DM risks in CumMHR Quartiles 2, 3, and 4 were 1.14 (1.01‒1.29), 1.17 (1.04‒1.32), 1.40 (1.25‒1.58), respectively, relative to Quartile 1. A significant interaction between CumMHR and cumulative high-sensitivity C-reactive protein (CumCRP) was observed (P-interaction: 0.0109). The diabetic risk in the highest quartile of CumMHR was higher (1.53 [1.28‒1.84]) when CumCRP < 1 mg/L, attenuated with increasing CumCRP levels (1 ~ 10 mg/L) and disappeared in CumCRP ≥ 10 mg/L. Hypertension, overweight, or smoking habits further modified the CumMHR-associated diabetic risk.ConclusionsCumulative MHR may be a promising supplement to hsCRP for more comprehensively assessing the influence of metabolic inflammation on T2DM susceptibility. For primary prevention, targeting high CumMHR, especially in cases at low risk of diabetes defined by traditional risk factors, may further help reduce the diabetic risk.

Molecular genetic etiology by whole exome sequence analysis in cases with familial type 1 diabetes mellitus without HLA haplotype predisposition or incomplete predisposition.

Familial transmission is observed in approximately 10% of cases with type 1 diabetes mellitus (T1DM). The most important gene determining susceptibility is the human leukocyte antigen complex (HLA) located on chromosome 6. More than 50 susceptible loci are associated with T1DM susceptibility have been identified in genes other than HLA. In this study, it was aimed to investigate the molecular genetic etiology by whole-exome sequence (WES) analysis in cases with familial T1DM with no or weakly detected HLA tissue type susceptibility. We aimed to identify new genes responsible for the development of type 1 diabetes and to reveal new genes that have not been shown in the literature before. Cases with at least one T1DM diagnosis in first-degree relatives were included in the study. In the first step, HLA DQ2 and DQ8 loci, which are known to be associated with T1DM susceptibility, were investigated by. In the second step, the presence of variants that could explain the situation was investigated by WES analysis in patients who were negative for both HLA DQ2 and HLA DQ8 haplotypes, HLA DQ2 negative, HLA DQ8 positive, and HLA DQ2 positive and HLA DQ8 negative patients. The mean age and duration of diabetes of the 30 cases (Girl/Male: 17/13) were 14.9±6 and 7.56±3.84 years, respectively. There was consanguineous marriage in 5 (16%) of the families. As a result of filtering all exome sequence analysis data of two cases with DQ2 (DQB1*02) (-) and DQ8 (DQB1*03:02) (-), seven cases with DQ2 (DQB1*02) (+) and DQ8 (DQB1*03:02) (-), and one case with DQ2 (DQB1*02) (-) and DQ8 (DQB1*03:02) (+), seven different variants in seven different genes were detected in five cases. The pathogenicity of the detected variants were determined according to the "American College of Medical Genetics and Genomics (ACMG)" criteria. These seven variants detected were evaluated as high-score VUS (Variants of unknown/uncertain significance). In the segregation study conducted for the mutation in the POLG gene detected in case 5, this variant was detected in the mother of the case and his brother with T1DM. Segregation studies are ongoing for variants detected in other affected individuals in the family. In conclusion, in this study, seven different variants in seven different genes were detected in five patients by WES analysis in familial T1DM patients with no or weak HLA tissue type susceptibility. These seven variants detected were evaluated as high-score VUS. POLG might be a novel candidate gene responsible for susceptibility to T1DM. Non-HLA genes directly responsible for the development of T1DM were not detected in any of the cases.

Genetic and Functional Effects of Adiponectin in Type 2 Diabetes Mellitus Development.

Diabetes mellitus (DM) is a common chronic metabolic disease, and the C57BLKsJ-db/db mice are good animal models for type 2 diabetes mellitus (T2DM). In this study, Western blotting and immunohistochemistry (IHC) were employed to examine the protein expression of adiponectin in the liver tissues of T2DM mice with different disease courses (4, 16, and 32 weeks). Adiponectin expression reduced in the liver tissues of T2DM mice in different disease courses. The genotypic and allelic frequencies of the adiponectin gene rs1063538 and rs2241766 single nucleotide polymorphisms (SNPs) in a Taiwanese population (570 T2DM patients and 1700 controls) were investigated. Based on the genetic distribution of the rs2241766 locus, the distribution frequency of the T allele in the T2DM group (72.8%) was higher than in the control group (68.8%). Individuals carrying the G allele had a 0.82-fold greater risk of developing T2DM than individuals carrying the T allele. Differences were evident in the genotypic and allelic distributions (p &lt; 0.05). Enzyme-linked immunosorbent assay (ELISA) was used to measure changes in serum adiponectin protein concentrations in the healthy population and in patients with T2DM. Serum adiponectin concentration in patients with T2DM was lower than in the control group. In summary, adiponectin was determined to be a T2DM susceptibility gene and may be involved in T2DM progression.

Association of rs2910164 in miR-146a with type 2 diabetes mellitus: A case-control and meta-analysis study.

ObjectiveSeveral studies have shown that miR-146a rs2910164 (C > G) is associated with type 2 diabetes mellitus (T2DM) susceptibility, but the results are still controversial. This study is divided into two parts, and one is to explore the relationship between miR-146a rs2910164 polymorphism and the genetic susceptibility of T2DM in Chinese Han population. Second, a meta-analysis on the basis of a larger sample size was used to determine whether this is a susceptibility gene for T2DM.MethodsA case–control study including 574 T2DM patients and 596 controls was used to evaluate the association of miR-146a rs2910164 polymorphism with the risk of T2DM in Chinese Han People. Then, we systematically searched studies investigating the correlation between miR-146a rs2910164 polymorphism and T2DM susceptibility published before April 2022 from PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure database, and a meta-analysis including six studies was carried out. The results were expressed by odds ratio (OR) and its 95% confidence interval (95% CI).ResultsIn a case–control study, we found that there were no statistical differences in genotype frequencies between T2DM and control group. Subgroup analysis showed that, compared with the CC genotype, CG + GG genotype was associated with a decreased risk of T2DM in the subgroup of individuals ≥ 65 years old (OR = 0.75; 95% CI: 0.58–0.98; P adjusted = 0.032) and BMI < 18.5 (OR = 0.16; 95% CI: 0.03–0.89; P adjusted = 0.037). In overall meta-analysis, significant heterogeneity was detected. No significant association between miR-146a rs2910164 polymorphism and T2DM was observed in all genetic models under random effects models. Subgroup analysis revealed that there was a significant difference in genotype frequencies between the T2DM and control group in recessive model (CC vs. CG + GG: OR = 1.79; 95% CI: 1.08–2.96; PQ = 0.307, I 2 = 4.0%) and homozygote model (CC vs. GG: OR = 1.79; 95% CI: 1.07–3.00; PQ = 0.216, I 2 = 34.7%) in Caucasians.ConclusionThe results of our study demonstrate that the miR-146a rs2910164 polymorphism might have ethnicity-dependent effects in T2DM and may be related to T2DM susceptibility in Caucasians.

Vitamin D Receptor Gene ApaI and TaqI Polymorphisms in Type 2 Diabetes among Saudi Population

Background: Variants of vitamin D receptor (VDR) gene have been linked to a variety of diseases, including metabolic syndrome, cancer, bone disease, and tuberculosis. The relationship between VDR gene mutations and the susceptibility of type 2 diabetes mellitus (T2DM) in different ethnic groups is yet unknown. Vitamin D and its receptor complex have a function in regulating β-cell insulin secretion as a transcription factor.&#x0D; Objectives: The goal of this study was to see if there is a link between VDR Apa1 and Taq1 polymorphisms and T2DM susceptibility in the Saudis of Makkah environ.&#x0D; Materials and Methods: DNA was separated from peripheral blood and genotyped in 110 healthy controls and 110 unrelated people with T2DM for the VDR ApaI (G/T) rs7975232 and TaqI (A/G) rs731236 single nucleotide polymorphisms (SNPs) using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique.&#x0D; Results: The distributions of genotypes and alleles of VDR ApaI and TaqI polymorphisms were statistically indifferent across the groups investigated (P &gt;0.05).&#x0D; Conclusion: These findings showed that polymorphisms in the VDR ApaI and TaqI genes may not be linked to T2DM risk in Saudis.

Cytokine gene variants of TNF-α and IL-10 in the propensity of type 2 diabetes in south Indian population

Chronic inflammation plays an important role in type 2 diabetes mellitus (T2DM), a common endocrinological pro-inflammatory disorder associated with insulin resistance. The objective of the present study is to see individual and combined effect of TNF-α (rs361525, rs1800629) and IL-10 (rs1800872, rs1800896) genes on T2DM susceptibility The genotyping was carried out in 200 T2DM patients and 200 healthy controls by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) using suitable primers. The results shown that TNF-α (GA of rs361525 & rs1800629) and IL-10 (AA of rs1800872 & GA of rs1800896) genes are significantly linked with T2DM development. The presence of AA-GA genotype combination for both TNF-α and IL-10 genes were elevating the risk of T2DM. Moreover, individuals bearing haplotypes AAAA, AACA and AAAG experience the increased risk of T2DM. Furthermore, gene-gene interaction analysis shown that TNF-α (GA of rs361525 & rs1800896) gene redundantly confer 3.4-fold elevated risk for T2DM. In gene-environment interaction, GA of TNF-α −1800896, W/H ratio and TG/HDL ratio were redundantly interacted each other and increase the risk of T2DM by 67-times. In conclusion, our results reveal that there is a significant association between foresaid TNF-α, IL-10 gene promoter polymorphisms and T2DM development. To the best of our knowledge this study is the first of its kind in the literature reporting the epistatic association of TNF-α (rs1800629G/A) gene with TG/HDL ratio and W/H ratio over IL-10 gene polymorphisms for T2DM susceptibility among south Indians.

Association of CYP7A1 and CYP2E1 Polymorphisms with Type 2 Diabetes in the Chinese Han Populations.

BackgroundType 2 diabetes mellitus (T2DM) is caused by diverse environmental and genetic risk factors. Previous studies have reported that cytochrome P450 (CYP) is a promising gene for T2DM. Therefore, we aimed to determine the effects of CYP7A1 and CYP2E1 polymorphisms on T2DM susceptibility among the Chinese Han population.MethodsA case-control study was conducted to assess the potential relationship of four polymorphisms (rs8192879, rs12542233, rs2070672 and rs2515641) with T2DM susceptibility in the Chinese population, involving 512 T2DM patients and 515 age- and gender-matched healthy individuals. We used the Agena MassARRAY platform to detect CYP7A1 and CYP2E1 polymorphisms. The relationship between genetic polymorphisms and T2DM risk was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models.ResultsAfter adjusting for age and gender, rs12542233 in the CYP7A1 gene was significantly associated with decreased T2DM risk (recessive: OR = 0.67, 95% CI = 0.49–0.91, p = 0.012; after FDR correction, p = 0.048). The CYP7A1 rs12542233 was associated with a reduced risk of T2DM in people over 59 years of age (p = 0.010). In the population with BMI ≤ 24 kg/m2, CYP7A1 rs12542233 was associated with an increased risk of T2DM (p < 0.05). In the population with BMI > 24 kg/m2, CYP2E1 rs2515641 can significantly reduce the risk of T2DM (p < 0.05). And rs8192879, rs2070672 and rs2515641 could significantly increase the risk of diabetes retinopathy in T2DM patients (p < 0.05). Furthermore, the Trs8192879Crs12542233 haplotype was significantly associated with T2DM (p = 0.019).ConclusionCYP7A1 and CYP2E1 polymorphisms may contribute to T2DM susceptibility in the Chinese Han population, especially in stratified analysis.

The Effect of PRKAA2 Variation on Type 2 Diabetes Mellitus in the Asian Population: A Systematic Review and Meta-Analysis.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing among Asians. The adenosine monophosphate-activated protein kinase (AMPK) increases T2DM risk through insulin resistance. Glucose levels are related to AMPK subunit α2 encoded by PRKAA2. This systematic review and meta-analysis aimed to analyse the association between PRKAA2 variation and T2DM risk. Publication search related to PRKAA2 and T2DM used PubMed, ProQuest, and ScienceDirect databases. Article selection based on inclusion and exclusion criteria only included Japanese and Chinese populations. This meta-analysis used five genotype models to estimate the effect of PRKAA2 variation and T2DM risk. Additionally, a fixed-effect model was selected to measure the pooled size effect if P > 0.05 or I2 < 50%. Qualitative analysis included four eligible studies, and meta-analysis included only two studies because both showed data concerning rs2746342 variation. Patients with G allele are 1.45 times more likely to have T2DM than patients with T allele (95% confidence interval [CI]: 1.20, 1.76; P: 0.0001). Notably, patients who had GG genotype have 1.96 times higher risk of T2DM compared with those with TT genotype (95% CI: 1.34, 2.87; P: 0.0005), dominant model (odds ratio [OR]: 1.75; 95% CI: 1.32, 2.31; P: 0.001), and recessive model (OR: 1.43; 95% CI: 1.01, 2.01; P: 0.04). PRKAA2 variation, especially in rs2746342, has an association with T2DM risk in the G allele, additive, dominant, and recessive models. G allele might be the most contributable factor in increasing T2DM susceptibility.

The genetic influence of PD-1/PD-L1 axis single nucleotide polymorphisms on the incidence of type 1 diabetes mellitus in pediatric Egyptian patients

BackgroundThe increasing prevalence of diabetes mellitus (DM) is one of the most challenging public health issues. The destruction of insulin-producing cells in the islets of Langerhans is the hallmark of type 1 diabetes mellitus (T1DM) as an autoimmune disease. In the current case–control study, the role of single nucleotide polymorphisms (SNPs) was investigated within the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitory axis and their association with T1DM susceptibility in a sample of Egyptian pediatric patients. The study included 80 T1DM pediatric patients and 76 healthy control subjects. The patients were recruited from Beni-Suef University Hospital’s Pediatric Endocrinology Outpatient Clinic. Genotyping of PD-1 SNP (rs 34819629) and PD-L1 SNPs (rs 2297137 and rs 4143815) was performed by TaqMan allelic discrimination technique via real-time polymerase chain reaction (RT-PCR). The patients were subjected to a thorough clinical examination and history taking.ResultGenotyping of PD-1 (rs 34819629) revealed that all of the enrolled patients and the control group inherited the same genotype (GG genotype). With regard to PDL-1 rs4143815 SNP and the risk of T1DM occurrence, our comparison did not reveal the presence of an association between the different genetic models (general, dominant, and recessive) of the SNP and the risk of T1DM (p = 0.078 and p = 0.055; for the general genetic model, p = 0.061 and p = 0.169 for the dominant and the recessive types, respectively). Regarding PDL-1 rs2297137 SNP, the results of this study demonstrated that the risk of T1DM was significantly associated with the recessive genetic model (p = 0.007) as the diabetic group’s predominant G allele was higher compared to the control group.ConclusionThe findings obtained supported the hypothesis that the predominant G allele of PD-L1 rs2297137 is associated with the development of T1DM. Chronic hyperglycemia and long-standing diabetes problems are linked to both PD-L1 SNPs (rs4143815 and rs2297137). Future studies with a more significant number of patients are required to support our results.

Association of Polymorphisms within HOX Transcript Antisense RNA (HOTAIR) with Type 2 Diabetes Mellitus and Laboratory Characteristics: A Preliminary Case-Control Study.

Type 2 diabetes mellitus (T2DM) is a complex heterogeneous disease resulting from the environment and genetic interactions. Lately, genetic association studies have shown that polymorphisms in long noncoding RNAs (lncRNAs) are associated with T2DM susceptibility. This preliminary study is aimed at investigating if HOX transcript antisense RNA (HOTAIR) polymorphisms contribute to T2DM development. Five hundred clinically diagnosed T2DM cases and 500 healthy controls were recruited from the southeast Iranian population. Genomic DNA was isolated from nucleated blood cells and genotyped for MspI (C/T) (rs920778) and AluI (A/G) (rs4759314) polymorphisms using the PCR-RFLP technique. For genotyping rs12826786 C/T and rs1899663 G/T variants, ARMS-PCR method was applied. Our findings indicated that HOTAIR rs920778 C/T, rs12826786 C/T, and rs4759314 A/G polymorphisms have a significant positive association with T2DM, while a negative association was observed between rs1899663 G/T T2DM susceptibility. Significant associations were also observed between rs920778 C/T and HDL-C as well as s4759314 A/G and both FBS and LDL-C in T2DM patients. Haplotype analysis indicated that the CGCG, CTTG, TGTA, and TTTG haplotypes of rs920778/rs1899663/rs12826786/rs4759314 significantly enhanced T2DM risk by 1.47, 1.96, 2.81, and 4.80 folds, respectively. No strong linkage disequilibrium was found between the four HOTAIR SNPs. We firstly reported that HOTAIR rs1899663 G/T, rs12826786 C/T, rs4759314 A/G, and rs920778 C/T polymorphisms might influence T2DM susceptibility by modulating different signaling pathways and could be regarded as potential prognostic markers in T2DM patients.

Association study of single nucleotide polymorphisms of AQP7 and AQP9 genes with type 2 diabetes mellitus among ethnic Han Chinese population

To assess the association of single nucleotide polymorphisms (SNP) of aquaporin 7 ( AQP7) and aquaporin 9 ( AQP9) genes and type 2 diabetes mellitus (T2DM) among ethnic Han Chinese population. A case-control study involving 1194 subjects with T2DM and 1274 non-diabetic mellitus (NDM) subjects were enrolled. Genotypes of three SNPs (rs3758269 of AQP7 gene, rs16939881 and rs57139208 of AQP9 gene) were determined by using a MassArray method. The association of the three SNPs with T2DM was assess, and the correlation of glucose and lipid metabolism parameters with various SNP genotypes in the NDM group was analyzed. The allelic and genotypic frequencies of the three SNPs did not differ significantly between the two groups (P>0.05). Nor was there significant difference between the two groups with different genetic models (P>0.05). No significant association of genotypes of AQP7 gene rs3758269, AQP9 gene rs16939881 and rs57139208 with glucose and lipid metabolism parameters were observed in the NDM group (P>0.05). The rs3758269 in AQP7 gene and rs16939881 and rs57139208 in AQP9 gene are not associated with the genetic susceptibility of T2DM among ethnic Han Chinese population.

Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis

Background and aimsThe association between insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the risk of type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to assess the effect of the ACE I/D gene polymorphism on T2DM in the Middle East and North Africa region (MENA region). Material and methodsOur data was extracted from PubMed, Science Direct, and the Web of Science. The predefined inclusion criteria included only the human case-control studies of English Peer-reviewed papers containing the data on genotype distributions of ACE I/D polymorphism and the T2DM risk. Review articles, meeting abstracts, editorials, animal studies, and studies not providing genotype distribution data or without sufficient data were excluded from this work. Results of this meta-analysis were expressed using odds ratios (OR) and 95% confidence intervals (CI). Indeed, the potential sources of heterogeneity and bias were examined by the Egger regression. ResultsOf 2755 identified articles, 10 studies were selected, including 2710 patients with T2DM and 2504 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and the D allele of ACE I/D gene polymorphism (OR = 1.97; 95% CI = 1.33–2.93, p = 0.0007), recessive (OR = 2.16; 95% CI = 1.27–3.67; p = 0.004), dominant (OR = 2.45; 95% CI = 1.54–3.91; p = 0.0001), homozygote (OR = 3.35; 95% CI = 1.78–6.29; p = 0.0001) and heterozygote comparisons (OR = 1.76; 95% CI = 1.07–2.88; p = 0.024). ConclusionOur result suggests that this polymorphism may contribute to the development of T2DM in the MENA Region. This result needs to be confirmed by future well-designed studies with larger sample sizes in diverse populations and ethnicities.

Association of KCNQ1rs2237892C ⟶ T Gene with Type 2 Diabetes Mellitus: A Meta-Analysis

Background Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in adults, causing high morbidity and mortality worldwide. In recent years, the prevalence of T2DM has been increasing significantly, and genome-wide association studies (GWAS) have shown that KCNQ1 significantly increases the risk of T2DM. Objective To find large-scale evidence on whether the KCNQ1rs2237892C⟶T gene polymorphism is associated with T2DM susceptibility. Methods A comprehensive review of the Chinese and English literature on the association of T2DM with KCNQ1rs2237892 is published by PubMed and Baidu Academic. The included literature was part or all of the studied loci which were evaluated for association with T2DM. Forest plots were made of the included literature to analyze the association of KCNQ1 with polymorphisms of the studied loci, and funnel plots and Egger's test were used to evaluate the publication bias of the selected included literature. Results Ten case-control studies including a total of 7027 cases and 8208 controls met our inclusion criteria. Allele (C allele frequency distribution) (OR: 1.19; 95% CI: 0.87,1.62; P < 0.00001), recessive (OR: 0.73; 95% CI: 0.45,1.18; P < 0.00001) genetic model under the full population was observed between KCNQ1rs2237892C⟶T gene polymorphism and T2DM without a significant relationship. In a stratified analysis by race, a meaningful association was found in non-Asian populations under the allelic genetic model, but no association was found in Asian populations. Conclusion This meta-analysis showed no significant association between the rs2237892 polymorphism of the KCNQ1 gene and the risk of T2DM.

Relationship of microRNA locus with type 2 diabetes mellitus: a case–control study

Type 2 diabetes mellitus (T2DM) is considered as a metabolic disease with hyperglycemia. Accumulating investigations have explored the important role of hereditary factors for T2DM occurrence. Some functional microRNA (miR) polymorphisms may affect their interactions with target mRNAs and result in an aberrant expression. Thus, miR variants might be considered as a biomarker of the susceptibility of T2DM. In this study, we recruited 502 T2DM cases and 782 healthy subjects. We selected miR-146a rs2910164 C>G, miR-196a2 rs11614913 T>C and miR-499 rs3746444 A>G loci and carried out an investigation to identify whether these miR loci could influence T2DM occurrence. In this investigation, a Bonferroni correction was harnessed. After adjustment, we found that rs2910164 SNP was a protective factor for T2DM (GG vs CC/CG: adjusted P = 0.010), especially in never drinking (GG vs CC/CG: adjusted P = 0.001) and BMI ≥24 kg/m2 (GG vs CC/CG: adjusted P = 0.002) subgroups. We also identified that rs11614913 SNP was a protective factor for T2DM in smoking subjects (CC/TC vs TT: adjusted P = 0.002). When we analyzed an interaction of SNP–SNP with the susceptibility tof T2DM, rs11614913/rs3746444, rs2910164/rs3746444 and rs11614913/rs2910164 combinations were not associated with the risk of T2DM. In summary, this study highlights that rs2910164 SNP decreases the susceptibility of T2DM, especially in BMI ≥24 kg/m2 and never drinking subgroups. In addition, we also identify that rs11614913 C allele decreases the susceptibility of T2DM significantly in smoking subgroup.

Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus.

Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.

Association of APOE genotype with lipid profiles and type 2 diabetes mellitus in a Korean population.

Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia and lipid metabolism. A previous genome-wide association study revealed the TOMM40-APOE region as novel locus for T2DM susceptibility. This association study was conducted to determine the genetic effects of APOE single nucleotide polymorphisms (SNPs) on T2DM susceptibility and lipid profiles in a Korean population. A total of 6 tagging SNPs, including rs7412 and rs429358, were selected for ε genotype analysis and genotyped in 1436 subjects, consisting of 352 T2DM patients and 1084 unaffected controls. Logistic regression analyses were conducted and there were no significant associations among the APOE 6 tagging SNPs, ε genotypes, and haplotypes with T2DM susceptibility. To investigate the association of the APOE tagging SNPs with the lipid profiles, a regression analysis was conducted. As a result, rs7412 was significantly associated with the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels (Pcorr = 2.30 × 10-5 and 3.39 × 10-13, respectively) in the unaffected controls. The ε2 allele and ε3 allele were significantly associated with the TC (Pcorr = 4.46 × 10-6 and 0.02, respectively) and LDL levels (Pcorr = 3.54 × 10-14 and 0.0006, respectively) in the unaffected controls. Further analysis of only the unaffected controls was conducted. As a result, the APOE alleles ε2 and ε3 showed a significant association with the TC and LDL levels (P < 0.05). The results of this study may help in understanding APOE polymorphisms and ε alleles and lipid profiles, which have been highly linked to T2DM, in a Korean population.