Type 2 Diabetes Mellitus Susceptibility Research Articles

Association of polymorphisms in CYP2C8 and CYP2C9 with susceptibility to type 2 diabetes mellitus in a Chinese population

AimsCYP2C8 and CYP2C9 are cytochrome P450 epoxygenases responsible for metabolizing arachidonic acid into epoxyeicosatrienoic acids (EETs). These EETs play a crucial role as lipid mediators with numerous beneficial effects in type 2 diabetes mellitus (T2DM). In this study, we aimed to investigate the association of CYP2C8 and CYP2C9 genetic variants with T2DM in a Chinese population. MethodsWe conducted genotyping for 9 tag single nucleotide polymorphisms (SNPs) in CYP2C8 and 10 tag SNPs in CYP2C9 based on HapMap Chinese and Japanese data. Subsequently, we genotyped these SNPs in a Chinese cohort comprising 3410 individuals with T2DM and 3401 healthy controls. Statistical analyses were performed to assess the association between these SNPs and T2DM. ResultsIn our study population, we observed that rs1819173, located within the CYP2C9 gene region, was significantly associated with T2DM. Notably, the presence of the A allele was found to be protective against T2DM, as indicated by an odds ratio of 0.840 (95 % confidence interval: 0.780–0.904, P = 3.04 × 10−6). Furthermore, specific haplotypes (GT and AT) involving rs2071426 and rs6583967 in CYP2C8 exhibited associations with T2DM (P = 0.049 and 0.038, respectively). Subsequently, we conducted an analysis of the association between rs1819173 and non-alcoholic fatty liver disease (NAFLD), revealing a significant correlation (OR = 0.764, 95 % CI: 0.629–0.928, P = 0.007). ConclusionOur research identified a genetic variants rs1819173 within CYP2C8 are significantly associated with T2DM susceptibility in the Chinese population.

Role of NQO1 Gene Involvement and Susceptibility of T2DM Among Saudi Arabia Population.

NQO1 disruption enhances susceptibility to oxidative stress during hyperglycemia and is a significant contributor to the development and progression of diabetes. Oxidative stress has been linked to several symptoms, including hyperglycemia, reactive oxygen species buildup, high blood pressure, and the expression of inflammatory markers. Therefore, the present research aimed to evaluate the genetic abnormality of NQO1 (rs1800566, C609T) gene polymorphism, expression, and vitamin-D level assessment among Type 2 diabetes mellitus (T2DM) patients. The study included 100 newly diagnosed T2DM cases and 100 healthy individuals as healthy controls. Total RNA was extracted from the whole blood using the TRIzol method, and further cDNA was synthesized, and expression was evaluated. There is a significant difference in NQO1 (rs1800566, C609T) genotype distribution among the T2DM patients and healthy controls (p = 0.04). Compared with the NQO1 CC wild-type genotype, the NQO1 CT heterozygous genotype had an odds ratio of 1.96 (1.08-3.55), and the NQO1 TT mutant type genotype had an odds ratio of 3.31 (0.61-17.77). Significantly decreased expression of NQO1 mRNA was observed with heterozygous CT (p < 0.0001) and homozygous mutant TT genotype (p = 0.0004), compared with homozygous wild-type CC genotype. NQO1 mRNA expression level was also compared with vitamin D levels among the T2DM patients. T2DM patients with vitamin D deficiency had 1.83-fold NQO1 mRNA expression, while vitamin D insufficient and sufficient T2DM cases had 3.31-fold (p < 0.0001) and 3.70-fold (p < 0.0001) NQO1 mRNA expression. It was concluded that NQO1 (rs1800566, C609T) CT and TT genotypes played a significant role in the worseness of type II diabetes mellitus, and decreased expression of NQO1 mRNA expression could be an essential factor for disease worseness as well as hypermethylation could be a factor for reduced expression leading to disease severity. The decreased NQO1 mRNA expression with heterozygous CT and mutant TT genotype associated with vitamin D deficiency may contribute to disease progression.

CTSG polymorphisms in Chinese children with type 1 diabetes mellitus.

Cathepsin G (CTSG) plays an important role in the regulation of immune processes. Accumulated studies show that CTSG is involved in the onset and development of type 1 diabetes mellitus (T1DM). As the genetic background of T1DM varies widely among populations, we aimed to study the relationship between genetic polymorphisms in CTSG and T1DM susceptibility in Chinese populations. A total of 141 patients with T1DM and 200 healthy controls were enrolled in the study. Serum CTSG expression was detected using enzyme-linked immunosorbent assay (ELISA). Genotyping of two selected single nucleotide polymorphisms (SNPs) (rs2236742 and rs2070697) of CTSG was performed using PCR and Sanger sequencing. CTSG expression in patients with T1DM was significantly higher than in the control group. Alleles C and T of CTSG SNP rs2236742 were increased in T1DM. No significant associations were found for the SNP rs2070697. Our results indicate that the CTSG rs2236742 allele (C/T) is associated with T1DM in Chinese children and may serve as a new biomarker for predicting T1DM susceptibility.

The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients

PurposeTo investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population. Materials/Methods76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants. ResultsAmong these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes. ConclusionThe study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.

A set of circulating microRNAs belonging to the 14q32 chromosome locus identifies two subgroups of individuals with recent-onset type 1 diabetes

Circulating microRNAs (miRNAs) are linked to the onset and progression of type 1 diabetes mellitus (T1DM), thus representing potential disease biomarkers. In this study, we employed a multiplatform sequencing approach to analyze circulating miRNAs in an extended cohort of prospectively evaluated recent-onset T1DM individuals from the INNODIA consortium. Our findings reveal that a set of miRNAs located within T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conducted additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named cluster A and cluster B. Remarkably, cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating miRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.

Association of common single-nucleotide polymorphism of HHEX with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease that occurs as a result of insulin resistance and low insulin production. T2DM involves many organ systems that include macro-vascular and micro-vascular complications. Several genome-wide association studies (GWAS) and candidate gene studies have suggested a large number of single nucleotide polymorphisms (SNPs) on several genes such as HHEX that were associated with T2DM susceptibility. The current study aims to look at the relationship between the risk of T2DM and the HHEX gene variant rs7923837. In this case-control study genotyping of rs7923837 of the HHEX gene was performed using the PCR-RFLP and Sanger sequencing method. Frequencies of GG genotype of rs7923837 polymorphism of HHEX among subjects with and without diabetes mellitus were 33.77% and 25.47% respectively. Corresponding prevalence for the AG genotype was 51.08% and 64.15% among subjects with and without diabetes mellitus respectively. The differences were not statistically significant (p = 0.08). Our study revealed that polymorphisms rs7923837 of HHEX were not associated with T2DM. The online version contains supplementary material available at 10.1007/s40200-024-01407-5.

Genetic Variants of CYP2C8 Gene Predisposition to Type 2 Diabetes Risk

Background: Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels due to insulin resistance or inadequate insulin secretion from pancreatic beta cells. The mitochondrial CYP2C8 gene, located on chromosome 10q24, encodes cytochrome P450 and spans 37 kb with nine exons. Genetic variants in this gene may influence T2DM susceptibility. Method: This study aimed to investigate the association between genetic polymorphisms in the CYP2C8 gene (rs1934953 and rs1934952) and the risk of T2DM in Iraqi patients. Blood samples were collected from 48 participants, including 24 T2DM patients and 24 healthy controls. DNA extraction, polymerase chain reaction (PCR), and sequencing were performed to analyze genetic variations. Statistical analysis was conducted using chi-square tests, logistic regression, and Hardy-Weinberg equilibrium calculations. Results: Analysis revealed that the rs1934953 variant in the CYP2C8 gene was associated with T2DM, with the A allele showing a protective effect (odds ratio: 0.840, 95% confidence interval: 0.780-0.904, P=3.04×10-6). Additionally, an interaction effect between rs1934953 in CYP2C9 and rs12766752 in CYP2C8 on T2DM risk was observed (P=0.003). Furthermore, rs1934953 showed significant association with high-density lipoprotein cholesterol (HDL-C). At the rs1934952 C/T locus, a transition type genetic mutation was detected, with the TT genotype considered a risk factor for T2DM, while the CC and CT genotypes were protective. The Hardy-Weinberg probability value for the patient group was 0.0321, indicating notable discrepancies in genotype distribution, while the healthy group showed no significant differences (Hardy probability: 0.2001). The TT genotype at rs1934953 was associated with a decreased risk of T2DM, while the CC and CT genotypes were potential risk factors. Conversely, at rs1934952, the CC and CT genotypes were protective against T2DM, while the TT genotype was associated with increased risk. Conclusion: in conclusion, the study indicates that there may be links between CYP2C8 gene variances and an increased chance of type 2 diabetes in Iraqi patients.

Genotype-based precision nutrition strategies for the prediction and clinical management of type 2 diabetes mellitus.

Globally, type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders. T2DM physiopathology is influenced by complex interrelationships between genetic, metabolic and lifestyle factors (including diet), which differ between populations and geographic regions. In fact, excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM, whereas habitual intakes of plant-based healthy diets usually exert a protective effect. Moreover, genomic studies have allowed the characterization of sequence DNA variants across the human genome, some of which may affect gene expression and protein functions relevant for glucose homeostasis. This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression, some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions. Also, novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations. Furthermore, progresses in other omics areas (epigenomics, metagenomics, proteomics, and metabolomics) are improving current understanding of genetic insights in T2DM clinical outcomes. Although more investigation is still needed, the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening, prevention, diagnosis, management, and prognosis of T2DM through precision nutrition.

Association analysis of MTHFR (rs1801133 and rs1801131) gene polymorphism towards the development of type 2 diabetes mellitus in Dali area population from Yunnan Province, China.

Type 2 diabetes mellitus (T2DM) is a common complex metabolic disorder that exhibits a strong genetic predisposition. 5,10-methylenetetrahydrofolate reductase (MTHFR) regulates folate metabolism, which has been proposed to be associated with T2DM, although the relationship is inconsistent among different geographical areas. This study aimed to investigate the effects of MTHFR C677T (rs1801133) and A1298C (rs1801131) loci polymorphisms on T2DM susceptibility in the population of the Dali area in Yunnan Province, China. This case-control study included 445 patients with T2DM and 272 healthy control individuals from the Dali area of Yunnan Province. Genotyping of the MTHFR gene polymorphisms was performed using the competitive allele-specific PCR (KASP) method. The effects of genetic variations of the MTHFR gene on T2DM risk were evaluated using odds ratios (OR) and 95% confidence intervals. The results of the present study revealed that the TT genotype (OR = 1.750, P = 0.030) and the T allele (OR = 1.252, P=0.047) at the MTHFR C677T locus were considerably associated with the increased odds of developing T2DM. In addition, the CC genotype (OR = 3.132, P=0.032) at the MTHFR A1298C locus also substantially increased the odds of developing T2DM. The T-A haplotype (OR = 1.305, P=0.030) of MTHFR C677T and A1298C exhibited the increased odds of developing T2DM. Biochemical index analyses showed that patients with T2DM who carried the CT or TT genotype of MTHFR C677T expressed substantially higher levels of fasting blood glucose (FBG), homocysteine (Hcy), and tumor necrosis factor-alpha (TNF-α) than those of the CC genotype. Moreover, the FBG and Hcy levels were considerably higher in patients with T2DM who carried the CC or AC genotype of MTHFR A1298C than those of the AA genotype. No obvious association was observed between these MTHFR polymorphisms and cardiovascular risk in T2DM. Our study suggests that the genetic variations of MTHFR C677T and A1298C are significantly associated with T2DM susceptibility in the population of the Dali area of Yunnan Province, China.

Genetic predisposition of LEPR (rs1137101) gene polymorphism related to type 2 diabetes mellitus – a meta-analysis

Background: Type 2 diabetes mellitus (T2DM) is a multifaceted disease appropriate to elevated blood glucose levels resulting from decreased insulin and beta-cell activity. Using a case–control methodology, researchers have examined the relationship between polymorphisms in LEPR and T2DM in a population from south India. Materials and Methods: We conducted a genetic analysis of 311 participants, and results were accomplished using a case-control study, a meta-analysis of previous studies on LEPR was conducted, and type 2 diabetes genotype distribution across various geographical regions Malaysians, Chinese Han, Kuwait, Iran, Mongolia, and Han Chinese, Greece, Saudi, India (North India, Punjabi), (South India, Tamilnadu). The study involved 254 prospective investigations, and nine association studies were preferred according to preset criteria. Studies were assessed for quality using the Hardy-Weinberg equilibrium (HWE) and the Newcastle–Ottawa Scale (NOS). An analysis of the genetic models was conducted to determine their relationship, statistical analysis was utilized to calculate odds ratios (ORs) and matching 95% confidence intervals (CIs). Results: The LEPR-rs1137101 polymorphism in the case-control study was associated with a significant increase in the risk of type 2 diabetes. A meta-analysis revealed a connection between LEPR gene polymorphism (rs1137101) and type 2 diabetes risk. Investigators might gain a more profound thought on the significance of the identified genetic variation and its impact on the chance of developing type 2 diabetes by verifying and strengthening previously reported findings. The model of fixed effects was chosen due to the low heterogeneity, and significant associations were observed in the allelic (OR = 0.79, 95% CI [0.70–0.87]), homozygote (OR = 0.58, 95% CI [0.46–0.72]), dominant (OR = 0.66, 95% CI [0.56–0.79]), and recessive (OR = 0.83, 95% CI [0.71–0.96]) genetic models. A Begg’s funnel plot and Egger’s test indicated no publication bias. These findings suggest that the rs1137101 variant in the LEPR gene has been linked to a higher risk of T2DM. Conclusions: A larger sample size, however, is required for further research, and consideration of potential confounding factors is needed to validate these associations. Understanding the implications of LEPR gene polymorphisms in T2DM susceptibility may contribute to personalized treatment strategies for patients with T2DM.

Association analysis between the VDR gene variants and type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is recognized as a complex metabolic which has affected the lives of millions of people around the world. Vitamin D receptor (VDR) gene polymorphisms have been suggested to be a vital contributor to the development of T2DM. However, the association between VDR gene polymorphisms and T2DM remains controversial.We have investigated the association between two VDR gene polymorphisms (rs731236 and rs1544410) and T2DM in an Iranian population. A total of 148 T2DM patients and 100 normal controls were recruited in this study. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to perform genotyping. The results of the present research revealed that the frequency of the rs731236 C allele was significantly higher in T2DM patients than in normal controls (p = 0.044). The CC genotype of rs731236 was connected with an increased risk of T2DM (OR = 2.85, 95% CI = 1.06-7.69, p = 0.039). However, no significant difference in the frequency of the rs1544410 C allele between T2DM patients and normal controls was observed (p = 0.918). Our findings were suggestive of the rs731236 polymorphism of the VDR as a risk factor for developing T2DM in the Iranian population, while rs1544410 polymorphism may not be associated with T2DM susceptibility. Further research is needed to approve these findings in other populations and to clarify the underlying mechanisms involved in such an association. The online version contains supplementary material available at 10.1007/s40200-023-01323-0.

Leptin Rs7799039 polymorphism is associated with type 2 diabetes mellitus Egyptian patients

Background Leptin (LEP) is an anti-obesity hormone that regulates food intake, energy expenditure, and glucose metabolism. The genetic variants in LEP and the LEP receptor (LEPR) gene may play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. The current study aimed to investigate the association of serum LEP levels, and LEP polymorphisms in LEP (rs7799039, 2548 G/A) with T2DM in Egyptian patients. Methods A total of 205 subjects were included in the present case-control study, consisting of 100 T2DM patients and 105 healthy controls. The anthropometric, psychometric, and biochemical measurements were taken from all the subjects. The genotyping of LEP gene variants was carried out by polymerase chain reaction TaqMan technology. Serum LEP levels were measured by the ELISA technique. Results T2DM patients had significantly elevated levels of glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), international normalisation ratio (INR), creatinine, urea, cholesterol, triglyceride (TG), and low-density lipoproteins (LDL) and significantly decreased high-density lipoprotein (HDL) compared to healthy subjects. serum LEP levels were significantly decreased p (<0.001) as compared to the control group. LEP gene SNP rs7799039 was associated with an increased diabetic risk with A allele being more frequent in T2DM patients than control subjects. The distribution of the AA genotype and GA genotype of LEP SNP rs7799039 was higher in the diabetic group than control one. In addition, AA + GA genotype carriers had significantly elevated HbA1c, FBS, PPBS, TG, and LDL levels and on the contrary, decreased serum LEP levels compared to GG homozygotes. Conclusion The genetic polymorphism rs7799039 showed a highly significant correlation with blood LEP. The co-dominant and dominant models of the LEP genetic polymorphism (rs7799039, 2548 G/A) were shown to have a significant correlation with complicated and uncomplicated diabetes individuals, but we have found that serum LEP levels were inversely related with control and diabetes patients. A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548 G/A) and serum LEP in patients and controls. LEP levels and its rs7799039 genetic variant may play a vital role in increasing T2DM susceptibility.

FTO gene variants (rs9939609, rs8050136 and rs17817449) and type 2 diabetes mellitus risk: A Meta-Analysis

Background and aimsThere is tremendous increase in type 2 diabetes mellitus (T2DM) worldwide. The impact of FTO gene polymorphisms on the risk of T2DM is not yet clear because of the controversial results of studies. This meta-analysis aimed to better clarify the association between three FTO gene polymorphisms SNPs (rs9939609, rs8050136 and rs17817449) and T2DM in a larger combined population worldwide. Material and methodsA comprehensive search on the PubMed, Science Direct, and Web of Science databases was conducted to identify investigations in relationship between different FTO gene polymorphisms (rs9939609, rs8050136 and rs17817449) and T2DM globally. Published papers from January 2007 to May 2023 were collected. Inclusion criteria are limited to human case-control studies published in English and peer-reviewed, which provided data on the genotype distributions of FTO gene polymorphisms and T2DM risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the results of the meta-analysis. Potential sources of bias and heterogeneity using Egger's regression analysis were also assessed. ResultsOf 234695 identified articles, forty-eight studies were selected including 36,051 patients with T2DM and 51,266 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and rs9939609 FTO gene polymorphism in the Allele contrast (A vs. T: OR = 1,30, 95% CI = 1.14; 1.48, P < 0,05, I2 = 0,94), Recessive model (AA vs. AT + TT: OR = 1,54, 95% CI = 1.19; 2.00, P < 0,05, I2 = 0,94), Dominant model (AA + AT vs. TT: OR = 1,26, 95% CI = 1.10; 1.45, P < 0,05, I2 = 0,89), homozygote model (AA vs. TT: OR = 1,60, 95% CI = 1.26; 2.03, P < 0,05, I2 = 0,90), and heterozygote model (AA vs. AT: OR = 1,43, 95% CI = 1.09; 1.88, P = 0,008, I2 = 0,93). we also found a significantly increased risk of T2DM susceptibility and rs8050136 FTO gene polymorphism under all models. For rs17817449 we did not find any association between with T2DM. ConclusionThe present meta-analysis confirms that rs9939609 and rs8050136 in the FTO gene are significantly associated with T2DM, while rs17817449 does not show any association.

The Genetic Diversity of Proteasome Genes in the T1DM Polish Population.

In the present study, the genetic variations in PSMB5 (rs11543947), PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) UPS gene cluster was investigated in type 1 diabetes and healthy donors in the Polish population. The study comprised 105 patients with type 1 diabetes mellitus (T1DM) and 214 controls. All were genotyped by PCR and restriction digestion analysis or Sanger sequencing. Rs1048990 and rs2348071 were found to be neutral to T1DM (p-value: 0.499 and 0.656, respectively). According to the multiple loci genotype (MLG) analysis, the major homozygote of the tested polymorphisms had a protective effect. The most common MLG in the T1DM group was characterised by simultaneous risk factors at rs11543947, rs2277460, rs2295826 and rs2295827 (pvalue: <0.0001 vs. MGL1). Multiple locus haplotype analysis revealed a similar dependence, with common alleles at all tested loci demonstrating a protective effect, and the rare alleles increasing T1DM risk (p-value: <0.0001 vs. MLH1). Our study suggests that the proteasome gene polymorphisms rs11543947, rs2277460, rs2295826, and rs2295827 could be potential markers for T1DM susceptibility in the Polish population.

MiR-499a rs3746444 A>G Polymorphism Is Correlated with Type 2 Diabetes Mellitus and Diabetic Polyneuropathy in a Romanian Cohort: A Preliminary Study.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, with little evidence available regarding Caucasians. The aim of the present study was to establish whether four miRNA SNPs (miR-27a rs895819 T>C, miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, and miR-499a rs3746444 A>G) are correlated with susceptibility to T2DM and/or diabetic polyneuropathy (DPN) in a Romanian population. A total of 167 adult T2DM patients and 324 age- and sex-matched healthy controls were included in our study. miRNA SNPs were detected by real-time PCR using a TaqMan genotyping assay. A significant association with T2DM was observed only for the miR-499a rs3746444 A>G SNP in all the tested models, and the frequencies of both the miR-499a rs3746444 AG and the GG genotypes were higher in the T2DM patients compared to the controls. No correlation was observed for the miR-27a rs895819 T>C, miR-146a rs2910164 G>C, or miR-196a2 rs11614913 C>T SNPs in any genetic model. When we assessed the association of these SNPs with DPN separately, we found a positive association for the miR-499a rs3746444 SNP in both codominant and dominant models (OR 6.47, 95% CI: 1.71-24.47; OR 2.30, 95% CI: 1.23-4.29, respectively). In conclusion, this study shows that miR-499a rs3746444 A>G may influence both T2DM and DPN susceptibility, with carriers of the GG genotype and the G allele being at an increased risk in the Romanian population.

Association of E23K (rs5219) polymorphism in the KCNJ11 gene with type 2 diabetes mellitus risk in Jordanian population

BackgroundThe E23K (rs5219) polymorphism in the potassium channel inward-rectifying subfamily J member 11 (KCNJ11) gene has been implicated with type 2 diabetes mellitus (T2DM) in several previous studies. However, contradictory findings observing a lack of association between this polymorphism and T2DM were also documented. For that reason, we investigated the E23K (rs5219) polymorphism relation to T2DM among Jordanians, analyzed its genotypic and allelic frequencies, and compared them with the findings among other populations. MethodsThe current study included 358 cases with T2DM and 326 controls without T2DM. The E23K (rs5219) polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. ResultsAccording to our findings, The E23K (rs5219) polymorphism was associated with T2DM susceptibility in Jordanians. The risk of developing T2DM was greater among the K allele carriers compared to the E allele carriers [P < 0.001]. Furthermore, T2DM was more common among those with the KK genotype than among those with the EE genotype [P: 0.008] after adjusting for gender, age, and body mass index. Based on the dominant model, both KK and EK genotypes showed an increased risk of T2DM than the EE genotype [P < 0.001] after adjusting for gender, age, and body mass index. ConclusionsThe polymorphism E23K (rs5219) is associated with susceptibility to T2DM in Jordanians.

Progonostic effect of GSTM1/GSTT1 polymorphism in determining cardiovascular diseases risk among type 2 diabetes patients in South Indian population.

Cardiovascular disease (CVD) is a significant complication of type 2 diabetes mellitus (T2DM), with oxidative stress playing a significant role. Glutathione S-transferase (GST) polymorphisms - GSTM1, GSTT1 - have been linked to CVD and T2DM. The role of GSTM1 and GSTT1 in CVD development among T2DM patients in the South Indian population is investigated in this study. The volunteers were grouped as Group 1: control, Group 2: T2DM, Group 3: CVD, and Group 4: T2DM with CVD (n = 100 each). Blood glucose, lipid profile, plasma GST, MDA, and total antioxidants were measured. GSTM1 and GSTT1 were genotyped using PCR. GSTT1 plays a significant role in the development of T2DM and CVD [OR 2.96(1.64-5.33), < 0.001 and 3.05(1.67-5.58), < 0.001] while GSTM1 null genotype was not associated with disease development. Individuals with dual null GSTM1/GSTT1 genotype had the highest risk of developing CVD [3.70(1.50-9.11), 0.004]. Group 2 and 3 individuals showed higher lipid peroxidation and lower total antioxidant levels. Pathway analysis further indicated that GSTT1 significantly affects GST plasma levels. GSTT1 null genotype may be considered a contributingfactor thatincreases the susceptibility and risk of CVD and T2DM in the South Indian population.

The Influence of SLC22A3 Genetic Polymorphisms on Susceptibility to Type 2 Diabetes Mellitus in Chinese Population.

Solute 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. We 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. The 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. SLC22A3 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.

A Pilot Study on the Prevalence of Transcription Factor 7-Like 2 Gene (TCFL2), Rs290487 in Ethnic Groups with Type 2 Diabetes Mellitus in Bayelsa State of Nigeria

The negative impact of type 2 diabetes mellitus (T2DM) on individuals, families, health system and the economic development as a whole, is an important justification for research in this field. The present study is a hospital-based case-control type to ascertain the genetic susceptibility of T2DM among a sample population of various ethnic groups resident in Bayelsa State, Nigeria. Also evaluated was the relationship between transcription factor 7-like 2 (TCFL2) rs12255372 and rs290487 genetic polymorphisms with development of T2DM. Genotyping of TCFL2 rs12255372 and rs290487 were carried out using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Among the indigenous groups, the allelic frequencies determined for the abnormal (CC) and the normal (TT) genotypes were 94.4 and 5.6 (%), respectively; whereas, the values 91.7 and 8.3 (%), in that other, were determined for the non-indigenous groups. A convincing significant difference was found between subjects with T2DMne and their counterpart controls within indigenous people of Bayelsa State with respect to confounders, including age (t=8.046, p&lt;0.00001), BMI (t =2.628, p&lt;0.0190), waist circumference (t=2.800, p=0.0091) and fasting blood sugar (t=3.212, p&lt; 0.0006). This study verified the association of TCFL2 rs290487 with the development of T2DM in indigenous and non-indigenous people in Bayelsa State. The risk conferred by the homozygous CC genotype was higher than that of the heterozygous TC state – a fact indicative of an additive model of inheritance.

Association of SLC11A1 polymorphisms with anthropometric and biochemical parameters describing Type 2 Diabetes Mellitus

Diabetes, a leading cause of death globally, has different types, with Type 2 Diabetes Mellitus (T2DM) being the most prevalent one. It has been established that variations in the SLC11A1 gene impact risk of developing infectious, inflammatory, and endocrine disorders. This study is aimed to investigate the association between the SLC11A1 gene polymorphisms (rs3731864 G/A, rs3731865 C/G, and rs17235416 + TGTG/− TGTG) and anthropometric and biochemical parameters describing T2DM. Eight hundred participants (400 in each case and control group) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) and amplification-refractory mutation system-PCR (ARMS-PCR) methods. Lipid profile, fasting blood sugar (FBS), hemoglobin A1c level, and anthropometric indices were also recorded for each subject. Findings revealed that SLC11A1–rs3731864 G/A, –rs17235416 (+ TGTG/− TGTG) were associated with T2DM susceptibility, providing protection against the disease. In contrast, SLC11A1–rs3731865 G/C conferred an increased risk of T2DM. We also noticed a significant association between SLC11A1–rs3731864 G/A and triglyceride levels in patients with T2DM. In silico evaluations demonstrated that the SLC11A2 and ATP7A proteins also interact directly with the SLC11A1 protein in Homo sapiens. In addition, allelic substitutions for both intronic variants disrupt or create binding sites for splicing factors and serve a functional effect. Overall, our findings highlighted the role of SLC11A1 gene variations might have positive (rs3731865 G/C) or negative (rs3731864 G/A and rs17235416 + TGTG/− TGTG) associations with a predisposition to T2DM.