Single Nucleotide Polymorphisms Rs7903146 Research Articles

Interaction of common variants of FTO gene and Dietary Inflammatory Index on obesity measures: Tehran Lipid and Glucose Study

BackgroundThis study aimed to examine the interaction of Dietary Inflammatory Index (DII) and fat mass and obesity-associated gene (FTO) single-nucleotide polymorphisms (SNPs) on change in obesity measures.MethodsA total of 4480...

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score.

Childhood dyslipidaemia is associated with the occurrence of cardiovascular diseases in adulthood, so evaluating whether an individual has a genetic predisposition to this pathology is of great importance for early action of prevention and treatment. This study aimed to evaluate the association between the FTO (rs9939609), MC4R (rs17782313) and MTMR9 (rs2293855) polymorphisms, the obesity-related genetic risk score and atherogenic risk in Brazilian children. This is a cross-sectional study conducted in 544 children aged 4-9 years in the city of Viçosa, Minas Gerais state, Brazil. The single nucleotide polymorphisms rs9939609, rs17782313 and rs2293855, were identified by the system TaqMan SNP genotyping and the obesity-related genetic risk score was determined. The lipid profile (serum total cholesterol [TC], high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol, triglycerides) was analysed and the atherogenic indices (Castelli I and II indices), atherogenic coefficient (AC), lipoprotein combined index (LCI) and plasma atherogenic index (PAI) were calculated. A semi-structured questionnaire was applied, obtaining data on the sociodemographic, economic and lifestyle characteristics of the children. Weight and height measurements were performed in all children, and body composition was evaluated by Dual-Energy X-ray Absorptiometry (DXA). 55.5% of the sample had dyslipidaemia, while 28.5% of the sample had at least one polymorphism and 2.2% had three polymorphisms. Children with the AG/AA genotypes in the rs2293855 polymorphism had lower HDL cholesterol levels and higher TC/HDL cholesterol, LDL/HDL cholesterol ratios and AC. Those with one or more polymorphisms (rs9939609, rs17782313 and rs2293855) in the genetic risk score had lower HDL cholesterol levels and higher TC/HDL cholesterol ratios, AC, LCI and PAI. In conclusion, the risk allele of the rs2293855 polymorphism and a higher obesity-related genetic risk score were positively associated with higher atherogenic risk in Brazilian children.

Association between IL-6 rs1800795 and IL-1β rs 16944 gene polymorphisms with clinical severity of COVID-19 patients in Surakarta, Central Java, Indonesia

Background: Cytokine plays a pivotal role in the pathogenesis of coronavirus disease 2019 (COVID-19). Cytokine storm is characterized by rapid elevation of an inflammatory circulating cytokine such as interleukin-6 (IL-6) and IL-1. However, according to evidence, genetic variables may affect the development and course of infectious diseases. Multiple genetic polymorphisms, mostly single-nucleotide polymorphisms (SNPs), have been linked to this setting's predisposition to viral infections. This study aimed to determine the frequency distribution of IL-6 SNPs rs1800795 and IL-1β SNPs rs16944 and rs1143627 gene polymorphisms and their association with the clinical severity of COVID-19 patients in Surakarta, Indonesia. This study aims to determine the association between IL-6 rs1800795 and IL-1β rs16944 with COVID-19 clinical severity. Methods: This study used a cross sectional design conducted at Universitas Sebelas Maret Hospital and centralized isolation of the Donohudan Hajj Dormitory from May to November 2021. A total of 120 COVID-19 patients were divided into 3 groups: asymptomatic, mild-moderate, and severe-critical. The detection of IL-6 SNPs rs1800795 and IL-1β SNPs rs16944 was carried out by quantitative PCR (qPCR) examination, and IL-6 and IL-1β were determined by the ELISA method. Result: There was no significant association between IL-6 SNPs rs1800795 (p=1.000) and IL-1β SNPs rs16944 (p=0.119) with clinical severity. In IL-1β SNPs rs16944 gene polymorphisms, the GG genotype was more commonly found in the asymptomatic group. AG genotype was commonly found in the symptomatic group (mild to critical). There was a significant association between IL-1β levels and clinical severity (p=0.03), whereas the association between IL-6 levels and clinical severity is not significant (p=0.103). Conclusion: There was a correlation between IL-1β levels with clinical severity. In IL-1β SNPs rs16944, the GG genotype may act as a protective factor, whereas the AG genotype may act as a factor that increases the clinical severity of COVID-19.

Minor alleles in the FTO SNPs contributed to the increased risk of obesity among Korean adults: meta-analysis from nationwide big data-based studies.

Many studies have revealed an association between fat mass and the obesity-related gene (FTO) and obesity. On the other hand, no meta-analysis was conducted with data from only Koreans. Therefore, this study performed a meta-analysis using Korean data to provide evidence for the association between FTO single nucleotide polymorphisms (SNPs) and the risk of obesity among Korean adults. Meta-analysis was finally conducted with data extracted from seven datasets of four studies performed on Korean adults after the screening passed. Five kinds of FTO SNPs (rs9939609, rs7193144, rs9940128, rs8050136, and rs9926289) were included, and the relationship between FTO SNPs and body mass index (BMI) was investigated using linear regression with an additive model adjusted for covariants, such as age, sex, and area. The minor alleles of FTO SNPs were associated with increased BMI (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.21-1.42). In sub-group analysis, FTO rs9939609 T>A was significantly associated with BMI (OR, 1.23; 95% CI, 1.06-1.42). The other FTO SNPs together were significantly associated with BMI (OR, 1.37; 95% CI, 1.25-1.49). The publication bias was not observed based on Egger's test. This meta-analysis showed that minor alleles in the FTO SNPs were significantly associated with an increased BMI among Korean adults. This meta-analysis is the first to demonstrate that minor alleles in the FTO SNPs contribute significantly to the increased risk of obesity among Korean adults using data from a Korean population.

FTO genotype was associated with breast cancer in HER2 negative patients.

The fat mass and obesity-associated (FTO) gene may influence the risk of breast cancer (BC). The single nucleotide polymorphisms (SNPs) of FTO gene may exert different impacts on different types of BC. In this study, we investigated the association between FTO SNP rs9939609 and the status of estrogen receptor (ER), progesterone receptor (PR), P53, and human epidermal growth factor receptor-2 (HER-2) in BC patients. Our case-control study was included 540 Iranian participants aged 35 to 70 (180 women with BC as the case group and 360 healthy controls). After genotyping for risk allele rs9939609 of the FTO gene, a logistic regression was applied to elucidate the association between FTO SNP rs9939609 and BC risk based on the receptor status. The number of HER-2 negative patients was significantly higher in FTO rs9939609 risk allele carrier group (61.5% vs. 41.4%, P<0.05). A significant association was found between BC and rs9939609 FTO gene polymorphism only in HER2 negative BC patients (OR=1.79, CI95%: 1.2-3.56, P=0.03). No association was identified between FTO rs9939609 polymorphism and the status of ER, PR, and P53. We indicated that FTO SNP rs9939609 can be a potential therapeutic target particularly in HER-2 negative BC cases. The importance of this risk allele in BC pathogenesis needs to be further highlighted.

Evaluation of the relationship between IL-6 gene single nucleotide polymorphisms and the severity of COVID-19 in an Iranian population.

BackgroundEmerged coronavirus disease 2019 (COVID-19) is a pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Disease severity is associated with elevated levels of proinflammatory cytokines, such as interleukin-6 (IL-6). Genetic polymorphisms in the regulatory regions of cytokine genes may be associated with differential cytokine production in COVID-19 patients. This study aimed to investigate the association between three potentially functional single-nucleotide polymorphisms (SNPs) in the promoter region of IL-6 and the severity of susceptibility to COVID-19 in an Iranian population.MethodsIn total, 346 individuals (175 patients with severe COVID-19 and 171 patients with mild COVID-19) were recruited for this cohort study. Genomic DNA was extracted from peripheral blood leukocytes of patients to determine the genotypes of three selected SNPs (rs1800795 (−174 G > C), rs1800796 (−572 G > C), and rs1800797 (−597 G > A)) in the promoter region of the IL-6 gene using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.ResultsThere were no significant differences in the genotype or allele distribution of selected SNPs (rs1800795 (−174 G > C), rs1800796 (−572 G > C), and rs1800797 (−597 G > A)) in the promoter region of the IL-6 gene in patients with severe COVID-19 and patients with mild COVID-19.DiscussionOur study indicated that these SNPs are not associated with COVID-19 severity in the Kurdish population from Kermanshah, Iran.

Association of rs7903146 TCF7L2, rs1042714 ADRB2 with the changes in body fat mass in different types of therapy of early carbohydrate metabolism disorders

BACKGROUND: Depending on the polymorphism of genes that that are involved in metabolism, the response of patients to different types of therapy may differ. Despite the potential effect of rs7903146 TCF7L2 and rs1042712 ADRB2 on changes in body composition in different types of therapy of early carbohydrate metabolism disorders, these associations haven’t been studied yet. AIM: To study the influence of rs7903146 TCF7L2, rs1042714 ADRB2 on changes in body fat composition in different types of therapy of early carbohydrate metabolism disorders.MATERIALS AND METHODS: The study involved patients with overweight or obesity and risk factors for Type 2 Diabetes development. All patients underwent genotyping with the real-time polymerase chain reaction, oral glucose tolerance test and bioimpedancemetry. Further, the patients were divided into two groups. First group kept a diet with the exclusion of simple and limitation of complex carbohydrates and fats. Second group took metformin in addition to the diet. Three months after bioimpedancemetry was performed again.RESULTS: The research involved 73 patients (the mean age 48±12 y.o., the mean BMI 34,27±6,18 kg/m2 ). The diet therapy group consisted of 47 people. Other 26 patients took metformin in addition to the diet. In group of diet, T allele carriers of rs7903146 TCF7L2 were characterized with more decrease in fat mass compared with CC homozygotes (- 7.90 ± 9.46% vs. -1.54 ± 8.98%, p = 0.027). CC genotype carriers of rs7903146 TCF7L2 in group of metformin and the diet had a tendency for more decrease in hip circumference compared with T allele carriers (-4.95 ± 3.34% vs. — 2.5 ± 2.96%, p = 0.064). Carriers of C allele in homozygous state of rs1042714 ADRB2, who took metformin with the diet, demonstrated more decrease in hip circumference (- 5.81 ± 3.00% vs. -2.50 ± 2.7%, p = 0.009), the tendency for decrease in fat mass (-8.28 ± 8.86% vs. — 3.20 ± 5.09%, p = 0.068) and waist circumference (-5.91 ± 4.29% vs. -3.03 ± 4.01 %, p = 0.091) compared with G allele carriers. The association of rs7903146 TCF7L2 and rs1042714 ADRB2 with changes in total body weight was not observed (p&gt; 0.05).CONCLUSION: Single nucleotide polymorphisms rs7903146 TCF7L2 and rs1042714 ADRB2 influence on body fat composition in patients with early carbohydrate metabolism disorders in various types of treatment.

Implication of KCNJ11 and TCF7L2 gene variants for the predisposition of type 2 diabetes mellitus in West Bengal, India

BackgroundPopulation-based Genome-wide association studies showed variants in KCNJ11 and TCF7L2 genes are associated with type 2 diabetes mellitus (T2DM). Our study was aimed to identify the association of common variants of these genes with T2DM and related traits in West Bengal, India. MethodsSix single nucleotide polymorphisms (SNPs) of two genes (KCNJ11- rs5219, rs5215, rs5213, and TCF7L2-rs7903146, rs12255372, rs10885409) were genotyped in 200 T2DM patients and 200 ethnically matched normal individuals. ResultsResults showed the association of four SNPs (rs5219, rs5213, rs7903146, and rs12255372) with T2DMwhere odd ratios (OR) were 1.46, 1.44, 1.48, and 1.42 respectively. Iindividuals carrying 4 risk alleles (T of rs7903146, T of rs12255372, A of rs5219, and G of rs5213) have 3 fold risk (p = 0.007, OR = 2.81; 95%CI: 1.32–5.98) of T2DM. We observed a significant association between individuals carrying 4 risk alleles and glycemic risk factors (fasting blood glucose, p-0.008 & postprandial blood glucose, p-0.007) as well as a cardiovascular risk factor (VLDL levels, p-0.036). ConclusionsOur study identified four common variants of KCNJ11 and TCF7L2 genes which areassociated with T2DM in the population of West Bengal, India.

Association of ADIPOQ Single-Nucleotide Polymorphisms with the Two Clinical Phenotypes Type 2 Diabetes Mellitus and Metabolic Syndrome in a Kinh Vietnamese Population.

PurposeGenetic factors play an important role in the development of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). However, few genetic association studies related to these disorders have been performed with Vietnamese subjects. In this study, the potential associations of ADIPOQ single nucleotide polymorphisms (SNPs) with T2DM and MetS in a Kinh Vietnamese population were investigated.Patients and MethodsA study with 768 subjects was conducted to examine the associations of four ADIPOQ SNPs (rs266729, rs1501299, rs3774261, and rs822393) primarily with T2DM and secondarily with MetS. The TaqMan SNP genotyping assay was used to determine genotypes from subjects’ DNA samples.ResultsAfter statistical adjustment for age, sex, and body mass index, the ADIPOQ SNP rs266729 was found to be associated with increased risk of T2DM under multiple inheritance models: codominant (OR = 2.30, 95% CI = 1.16–4.58), recessive (OR = 2.17, 95% CI = 1.11–4.26), and log-additive (OR = 1.32, 95% CI = 1.02–1.70). However, rs1501299, rs3774261, and rs822393 were not associated with risk for T2DM. Additionally, rs266729, rs3774261, and rs822393 were statistically associated with MetS, while rs1501299 was not. Haplotype analysis showed a strong linkage disequilibrium between the SNP pairs rs266729/rs822393 and rs1501299/rs3774261, and the haplotype rs266729(G)/rs822393(T) was not statistically associated with MetS.ConclusionThe results show that rs266729 is a lead candidate SNP associated with increased risk of developing T2DM and MetS in a Kinh Vietnamese population, while rs3774261 is associated with MetS only. Further functional characterization is needed to uncover the mechanism underlying the potential genotype–phenotype associations.

Clinical aspects of the effectiveness of metformin therapy in combination with a low-calorie diet in patients with type 2 diabetes mellitus with various variants of the TCF7L2 gene polymorphism

The TCF7L2 gene is one of the new markers associated with the development of type 2 diabetes mellitus (DM). Evaluation of the effect of TCF7L2 gene polymorphisms on the effectiveness of hypoglycemic therapy will allow an individual approach to the choice of methods for treating type 2 DM in their carriers. The aim of the research was to study the effect of carriage of TCF7L2 gene polymorphisms on glycemic control parameters in patients with type 2 DM receiving metformin glucose-lowering therapy in combination with a low-calorie version of the standard diet. Material and methods. The study included 55 patients with type 2 DM (mean age 59.9±6.9, BMI 44.3±8.2 kg/m2) receiving metformin monotherapy at a dosage of 1500-2000 mg/day in combination with a low-calorie variant of the standard diet (1730±130 kcal/day). The frequency of occurrence of polymorphisms rs7903146/rs12255372 of the TCF7L2 gene was studied. The indicators of glycemic and metabolic control, anthropometric parameters and body composition were evaluated. Results. The frequency of occurrence of the T-allele of both single nucleotide polymorphisms rs7903146 and rs12255372 of the TCF7L2 gene among patients was 38.2%. Among carriers of the T-allele rs7903146 of the TCF7L2 gene, 72% of patients responded to therapy, showing a statistically significant decrease in the level of fasting glycemia by an average of 16.2±1.6% from the baseline, while among carriers of the CC genotype - 10.5±1.5% (p=0.017). There were no statistically significant changes in glycemic control indicators on hypoglycemic therapy during 7 months of observation, both in the group of T allele and CC genotype carriers. Conclusionss. An improvement in glycemic control was established in patients with type 2 DM among carriers of the T allele rs7903146 of the TCF7L2 gene during metformin therapy in combination with a low-calorie standard diet. The study of TCF7L2 gene polymorphism in combination with indicators of glucose metabolism makes it possible to predict the effectiveness of hypoglycemic therapy with great accuracy.

Are single nucleotide polymorphisms rs7903146 and rs12255372 in transcription factor 7-like 2 gene associated with an increased risk for gestational diabetes mellitus in Egyptian women?

BackgroundGenetic variants in the transcription factor 7-like 2 (TCF7L2) gene are related with type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) in various populations, but there are not enough statistics regarding GDM among Egyptian women. We aimed by this study to evaluate the effect of two polymorphisms of rs7903146 and rs12255372 in the TCF7L2 gene with the development of GDM among Egyptian women. ResultsWe enrolled 114 pregnant women with normal glucose tolerance and 114 with GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines. We gathered records on blood pressure, body mass index (BMI), blood glucose level, hemoglobin A1C (HbA1c), and lipid profile. The genotyping of rs7903146 and rs12255372 polymorphisms was carried out using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). The statistical significance of prepregnancy BMI, fasting blood sugar (FBS), HbA1c, low-density lipoprotein (LDL), and total cholesterol (Tch) was higher, P < 0.001, in GDM women in comparison to pregnant women without GDM. CT and TT genotypes in rs7903146 SNP were 46.5% vs. 54%, P <0.04, OR; CI = 1.9 (1.0 to 3.78); TT carriers were 37.7% vs. 9.6%, P <0.001, OR (CI) = 8.9 (3.7–21.1), respectively. For the TCFL2 gene rs12255372 SNP, GT carriers were 48.2% vs. 39.5%, P= 0.004, OR (CI) = 2.3 (1.3–4.2), while TT carriers were 24.6% vs. 7.9%, P < 0.001, OR (CI) = 6 (2.5–14.3). ConclusionThe study showed there is a significantly higher incidence of CT/TT genotypes in rs7903146 SNP and GT/TT genotypes in rs12255372 SNP in TCF7L2 gene among GDM women in comparison to healthy pregnant women (controls).

Serum spexin, adiponectin and leptin levels in polycystic ovarian syndrome in association with FTO gene polymorphism.

Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinopathy among reproductive-aged women and related with body mass and insulin resistance. Adipocytokines produced by adipose tissue seems to take part in the hormonal and metabolic alterations that arise in PCOS. Fat mass and obesity associated (FTO) gene is linked with body mass index (BMI) and diabetes. Aims - To investigate the association between fat mass related adipocytokines and single nucleotide polymorphisms (SNPs) (rs9939609 T/A) in the FTO gene in women with PCOS. Study design - Cross-sectional study MATERIAL AND METHODS: FTO+rs9939609 gene polymorphism and serum spexin, adiponectin and leptin levels were determined in 91 PCOS women and 86 healthy controls. Study participants were subdivided according to BMI and comparisons were made within each group. Serum spexin levels were not differed between study groups. Serum levels of adiponectin were found to be decreased in PCOS women with BMI lower than 25 kg/m2 (10.1 ± 5.6 vs 14.1 ± 9.1, p = 0.015). Serum leptin levels were elevated in obese PCOS women compared to healthy control group (2197.9 ± 596.3 pg/mL vs 1535.9 ± 812.1 pg/mL, p = 0.001). The prevalence of A risk allele of SNP rs9939609 was more frequent in PCOS patients than in the control group. PCOS risk was found to increase 3 times more in AA genotype when compared with TT genotype (OR = 3.04 95% CI: 1.243-7.309; p = 0.013). Serum adiponectin and leptin levels may serve as independent markers for PCOS diagnosis. Moreover, the FTO+rs9939609 gene polymorphism increase susceptibility to PCOS development independent from serum adipocytokine levels.

Association of Single Nucleotide Polymorphism rs2228570 with Lumbar Disc Degeneration: A Case-Control Study and Meta-Analysis.

ObjectiveTo examine the association between single nucleotide polymorphisms (SNPs) rs2228570, rs731236, rs7975232, and rs1544410 and lumbar disc degeneration (LDD) predisposition.MethodsA search strategy was carried out, and the data were extracted after being chosen by the inclusion and exclusion criteria. Pooled odds ratios and 95% confidence intervals were calculated to assess the association between the aforementioned SNPs and LDD under allelic, dominant, recessive, heterozygous, and homozygous genetic models. In addition, a case–control study involving 46 LDD cases and 45 controls was also performed in the analysis to verify the result.ResultsA total of 17 studies were included in this meta-analysis. The pooled results did not show any association between vitamin D receptor (VDR) gene polymorphisms and LDD. But, interestingly, in subgroup analysis, the rs2228570 polymorphism was associated with LDD under the allelic (OR = 0.70, 95% CI = 0.56–0.87, p = 0.002), recessive (OR = 0.60, 95% CI = 0.43–0.84, p = 0.003), and homozygous (OR = 0.47, 95% CI= 0.28–0.79, p = 0.004) genetic models in the Asian population. SNPs rs731236 and rs7975232 still did not show any obvious association. We obtained a similar result from the case–control study: rs2228570 had an obvious relationship with LDD under allelic and homozygous genetic models. At the same time, we found that rs2228570 was also associated with the degree of low back pain (visual analogue scale, VAS score) in LDD population.ConclusionSNP rs2228570 was significantly associated with LDD predisposition and the degree of low back pain in the Asian population.

Lack of association between single nucleotide polymorphisms in TCF7L2 and T2DM in the Chinese Yao population: A case-control study.

Single-nucleotide polymorphisms (SNPs) in the transcription factor 7-like 2 (TCF7L2) gene have been identified to be associated with the susceptibility to type 2 diabetes mellitus (T2DM) in various populations worldwide, but the results in Chinese are conflicting, and no data are available about the Liannan Yao population. Therefore, this study aimed to investigate the association of the TCF7L2 gene polymorphisms (rs12255372, rs7903146, rs7901695, rs11196205, and rs7895340) with T2DM in the Yao population living in the rural areas in the Liannan Yao Autonomous County.This was a case-control study of 28 subjects with T2DM or prediabetes and 52 non-T2DM controls, all from the Chinese Yao population and recruited between January 2019 and June 2020. Patients with T2DM and prediabetes were grouped as the case group. The five SNPs (rs12255372, rs7903146, rs7901695, rs11196205, and rs7895340) were examined by polymerase chain reaction and direct genomic DNA sequencing in case and control groups.The subjects in case group were older than the controls (55±14 vs 48 ± 15 years, P = .047), had higher FBG levels (9.31 ± 5.43 vs 4.09 ± 0.81, P < .001), higher TC (5.79 ± 1.29 vs 5.13 ± 1.18 mmol/L, P = .025), and higher triglycerides (2.94 ± 2.04 vs 1.86 ± 1.39 mmol/L, P = .003). The genotypic distribution for each of the SNPs was in agreement with the Hardy-Weinberg equilibrium. There were no statistically significant differences in the distributions of genotypes or alleles at all five SNPs of the TCF7L2 gene between the case and control groups (all P > .05).TCF7L2 SNPs were not associated with T2DM in the Liannan Yao population.

Statistical meta-analysis to investigate the association between the Interleukin-6 (IL-6) gene polymorphisms and cancer risk.

A good number of genome-wide association studies (GWAS), including meta-analyses, reported that single nucleotide polymorphisms (SNPs) of the IL-6 gene are significantly associated with various types of cancer risks, though some other studies reported insignificant association with cancers, in the literature. These contradictory results may be due to variations in sample sizes and/or deficiency of statistical modeling. Therefore, an attempt is made to provide a more comprehensive understanding of the association between the IL-6 gene SNPs (rs1800795, rs1800796, rs1800797) and different cancer risks, giving the weight on a large sample size, including different cancer types and appropriate statistical modeling with the meta-dataset. In order to attain a more reliable consensus decision about the association between the IL-6 gene polymorphisms and different cancer risks, in this study, we performed a multi-case statistical meta-analysis based on the collected information of 118 GWAS studies comprising of 50053 cases and 65204 control samples. Results from this Meta-analysis indicated a significant association (p-value < 0.05) of the IL-6 gene rs1800796 polymorphism with an overall increased cancer risk. The subgroup analysis data based on cancer types exhibited significant association (p-value < 0.05) of the rs1800795 polymorphism with an overall increased risk of cervical, liver and prostate cancers; the rs1800796 polymorphism with lung, prostate and stomach cancers; and the rs1800797 polymorphism with cervical cancer. The subgroup analysis of ethnicity data showed a significant association (p-value < 0.05) of an overall cancer risk with the rs1800795 polymorphism for the African and Asian populations, the rs1800796 polymorphism for the Asian only and the rs1800797 polymorphism in the African population. Comparative discussion showed that our multi-case meta-analyses received more support than any previously reported individual meta-analysis about the association between the IL-6 gene polymorphisms and cancer risks. Results from this study, more confidently showed that the IL-6 gene SNPs (rs1800795, rs1800796 and rs1800797) in humans are associated with increased cancer risks. Therefore, these three polymorphisms of the IL-6 gene have the potential to be evaluated as a population based rapid, low-cost PCR prognostic biomarkers for different types of cancers diagnosis and research.

Relationship between TP53 and interleukin-6 gene variants and the risk of types 1 and 2 diabetes mellitus development in the Kermanshah province.

Diabetes mellitus (DM) is a metabolic disorder that results from insufficient secretion or insulin resistance, or both. Insulin secretion deficiency leads to chronic hyperglycemia along with impaired metabolism of proteins, lipids, and carbohydrates. This study aimed to investigate the TP53 gene SNP (single nucleotide polymorphism) rs1042522 genotype and the interleukin-6 (IL-6) gene SNP rs1800795 genotype in DM and control groups. This study was performed on 70 patients with type 1 DM, 100 patients with type 2 DM without related complications, 66 control subjects for type 1 DM, and 95 control subjects for type 2 DM. The control groups were matched regarding age and gender and did not have a familial relationship with the patient groups. All the subjects were residents of Kermanshah, located in the western part of Iran. Polymorphisms of TP53 and IL-6 genes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Lipid profile, fasting blood glucose, and HbA1c were measured using the ELISA and immunoturbidometric methods. The frequency of genotypes (CC, CG, GG) of the TP53 gene codon 72 in type 1 DM and its control group were significantly different (P= 0.013). Likewise, the frequency of genotypes (CC, CG, GG) of the TP53 gene codon 72 was significantly different between type 2 DM and control groups (P <0.001). The frequency of genotypes (GG, GC, CC) of G174C polymorphisms in the IL-6 gene was different between type 1 DM and control group as well as between type 2 DM and its control group, but it was not statistically significant. SNP rs1042522 genotypes in the dominant form (CG + GG vs. CC) (OR= 3.880; P < 0.001) and alleles G vs. C alleles (OR= 0.384; P < 0.001) increased the risk of type 2 DM significantly. There was no significant difference between type 1 and type 2 DM groups and respected control groups regarding the frequency of the IL-6 gene SNP rs1800795 alleles. The G allele of SNP rs1042522 encoding the TP53 gene increases the risk of developing DM in the population of the Kermanshah province, Iran.

The association of interieukin-6 polymorphism (rs1800795) with microvascular complications in Type 2 diabetes mellitus.

Objectives: To evaluate the effects of the single-nucleotide polymorphism (SNP) rs1800795 in interieukin-6 (IL-6) gene on diabetic microvascular complications of Type 2 diabetes mellitus (T2DM), using statistical meta-analysis.Methods: Literature pertaining to the relationship between the SNP rs1800795 and microvascular complications of T2DM including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and foot disease was retrieved from PubMed, Web of Science Knowledge and SinoMed databases. Original information was analyzed using Stata 12.0, including meta-analysis statistics, test for heterogeneity, evaluation of publication bias and sensitivity. Subgroup analysis was conducted to assess the effect of specific factors on the corresponding results.Results: In total, 14 eligible articles were obtained. The SNP rs1800795 in IL-6 gene is not correlated with risk of microvascular complications in T2DM. Among the original literature, a genetic model (OR = 1.071, 95% CI: 0.681–1.685, P=0.767), an allelic genetic model (OR = 1.010, 95% CI: 0.959–1.063, P=0.703), a heterozygote genetic model (OR = 1.107, 95% CI: 0.916–1.339, P=0.292), a dominant genetic model (OR = 1.108, 95% CI: 0.885–1.387, P=0.372), and a recessive genetic model (OR = 0.978, 95% CI: 0.646–1.478, P=0.917) were included respectively. In the subgroup analysis by types of diabetic microvascular complications, we found no correlation between the SNP rs1000795 polymorphism and complications of T2DM in either the homozygote genetic model or the allelic genetic model (P<0.05).Conclusion: Our results demonstrate that rs1800795 polymorphism in IL-6 gene is not correlated with the susceptibility of microvascular complications of T2DM.

FTO gene–lifestyle interactions on serum adiponectin concentrations and central obesity in a Turkish population

The aim of the study was to investigate whether lifestyle factors modify the association between fat mass and obesity-associated (FTO) gene single nucleotide polymorphisms (SNPs) and obesity in a Turkish population. The study included 400 unrelated individuals, aged 24-50 years recruited in a hospital setting. Dietary intake and physical activity were assessed using 24-hour dietary recall and self-report questionnaire, respectively. A genetic risk score (GRS) was developed using FTO SNPs, rs9939609 and rs10163409. Body mass index and fat mass index were significantly associated with FTO SNP rs9939609 (p = 0.001 and p = 0.002, respectively) and GRS (p = 0.002 and p = 0.003, respectively). The interactions between SNP rs9939609 and physical activity on adiponectin concentrations, and SNP rs10163409 and dietary protein intake on increased waist circumference were statistically significant (P interaction = 0.027 and P interaction = 0.044, respectively). Our study has demonstrated that the association between FTO SNPs and central obesity might be modified by lifestyle factors in this Turkish population.

Lack of association between interleukin 13, interleukin 4 receptor alpha, andMS4A2 gene polymorphisms and asthma in adult Saudis

Objectives: Several genes, including interleukin-13 (IL13), MS4A2, and IL 4 receptor alpha (IL4Rα), have been shown to associate with the inflammatory process in asthma. We investigated the possible association between asthma and five single-nucleotide polymorphisms (SNPs) in the IL13, IL4Rα, and MS4A2 gene in comparison with the level of the IL-13 protein in the Saudi asthmatics and controls. Subjects and Methods: The study group included 50 adult asthmatic patients and 50 normal healthy controls. Blood was extracted, and DNA was prepared. Genotyping was performed on DNA using direct sequencing for four SNPs (rs20541, rs1800925, rs1801275, and rs569108), and real-time polymerase chain reaction allelic discrimination to study rs1805010 polymorphism. Levels of IL-13 were measured in plasma using (enzyme-linked immunosorbent. Genotype and allele frequencies were calculated for each SNP. Results: The results showed that GG genotype of rs1801275 in the IL4Rα gene was more common in the asthmatic patients compared to the control group, though the results did not show any statistical significance (P G transition nonsynonymous mutation, resulting in the substitution of glutamine by arginine showed an association, but it was statistically not significant. Interestingly, presence of the mutant allele of both SNPs of IL-13 gene significantly elevated IL-13 level. Comparison of the Saudi results with those of other populations, showed several significant differences. We conclude that further more detailed studies are necessary in Saudis to identify the contribution of SNPs in cytokine genes in asthma development.

No Significant Effects of IL-6 and IL-13 Gene Variants on Tuberculosis Susceptibility in the Chinese Population.

Tuberculosis (TB) is an intricate infectious disease that causes a large number of deaths in the population. Interleukin (IL)-6 and IL-13 play functional roles in host resistance to Mycobacterium tuberculosis infection. Our aim in this study was to explore the association of IL-6 and IL-13 polymorphisms with TB susceptibility in the Western Chinese Han population. The case and control groups comprised 900 TB patients and 1534 healthy controls, respectively, and four single-nucleotide polymorphisms (SNPs) were genotyped in IL-6 and five SNPs in IL-13 through the improved multiplex ligation detection reaction method. We found no genetic variants in the IL-6 or IL-13 genes that were related to TB susceptibility in the analysis of alleles, genotypes, genetic models, and TB clinical subtypes, except for a trend toward low pulmonary tuberculosis and extrapulmonary tuberculosis susceptibility for the SNPs rs1295686 and rs20541. Our study did not find a link between IL-6 and IL-13 polymorphisms and TB susceptibility in the Western Chinese Han population. Therefore, our present data revealed the challenge of applying IL-6 and IL-13 SNPs as genetic markers for TB and that increased sample sizes and additional races are needed for further studies.