Insertion and deletion polymorphism in the alpha-2B adrenoceptor gene in pregnant women ripens gestational diabetes mellitus

There are no earlier studies that reported the association of the 12Glu9 polymorphism in the alpha-2B adrenoceptor (ADRA2B) gene with gestational diabetes mellitus (GDM). We examined the potential association between the ADRA2B gene insertion/deletion (I/D) polymorphism in the Saudi population with GDM. Pregnant women with GDM have been reported to exhibit the same susceptibility as that observed in type 2 diabetes mellitus (T2DM). We have selected I/D polymorphism of the ADRA2B gene located in chromosome 2q11.1 that has been extensively related to T2DM and cardiovascular diseases. This case–control study was conducted with 200 GDM and 300 non-GDM pregnant women. Genotyping of I/D polymorphism was performed by conventional PCR method. Biochemical analyses were found to be significantly different between GDM and non-GDM subjects (p < 0.05). Genotype (ID + DD vs II, p = 0.0002) and allele (D vs I, p = 0.0002) frequencies of the 12Glu9 polymorphism were found to be statistically significant. However, a significant difference was found between allele and genotypes of I/D polymorphism of the ADRA2B gene or the clinical characteristics of the subjects. Our results obtained in this study indicate the ADRA2B gene in the Saudi women was associated with the development of GDM.     

A Meta-Analysis of the Association between the CC Chemokine Ligand 5 (CCL5) -403 G>A Gene Polymorphism and Tuberculosis Susceptibility

Aim

Many case-control studies have been performed in the recent past to investigate the association between CCL5 -403 G>A (rs2107538) gene polymorphism and tuberculosis (TB) susceptibility in various ethnic groups. However, these studies have produced inconsistent and contradictory results. In the present study, meta-analysis was performed to assess the association between CCL5 -403 G>A polymorphism and TB risk.

Methodology

Quantitative synthesis was done for the published studies based upon association between CCL5 -403 G>A polymorphism and TB risk from PubMed (Medline), EMBASE web search. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models.

Results

A total of six studies comprising 1638 confirmed TB cases and 1519 healthy controls were included in this meta-analysis. Variant A allele (A vs. G: p = 0.035; OR = 1.301, 95% CI = 1.019 to 1.662) and variant homozygous (AA vs. GG; p = 0.001; OR = 1.520, 95% CI = 1.202 to 1.923) carriers were significantly associated with TB susceptibility. Similarly, recessive model (AA vs. GG+GA: p = 0.016; OR = 1.791, 95% CI = 1.117 to 2.873) also indicated increased TB risk. Whereas, heterozygous (GA vs. GG: p = 0.837; OR = 1.028, 95% CI = 0.791 to 1.335) and dominant (AA+GA vs. GG: p = 0.222; OR = 1.188, 95% CI = 0.901 to 1.567) models failed to show increased risk of developing TB.

Conclusions

This meta-analysis suggests that there is a significant association between the CCL5 -403 G>A polymorphism and increased risk of TB. However, larger well-designed epidemiological studies with stratified case control and biological characterization may be helpful to validate this association.     

Contribution of genetic variant identified in HHEX gene in the overweight Saudi patients confirmed with type 2 diabetes mellitus

BackgroundThe rs7932837 polymorphism in the Hematopoietically expressed homeobox (HHEX) gene was discovered through genome-wide association studies and is a promising candidate for type 2 diabetes mellitus (T2DM), which is one of the risk factors for obesity and other complications. T2DM has been identified as a heterogeneous and multifactorial disease characterized by insulin resistance and secretion.AimThe aim of this study was to investigate the rs7932837 polymorphism in the HHEX gene in overweight patients diagnosed with T2DM in the Saudi Population.MethodsIn this case-control study, one hundred T2DM cases and 100 controls were selected based on inclusion and exclusion criteria. Genotyping was performed with polymerase chair reaction-restriction fragment length polymorphism analysis and statistical analysis was performed between T2DM cases and controls for clinical characteristics, genotype and allele frequencies and multiple logistic regression analysis.ResultsIn this study, T2DM cases were compared with healthy control subjects. Clinical characteristic analysis revealed the statistical analysis between age, weight, BMI, FBG, HDL-c, TC, TG and family history (p < 0.05). HWE analysis was in the accordance (p < 0.05). The rs7932837 polymorphism in the recessive model showed the positive association (AA + AG vs AA: 2.22 [1.25–3.96] & p = 0.006) and none of the genotypes or alleles were in the statistical association. Multiple logistic regression analysis revealed positive association with age, BMI and FBG (p < 0.05).ConclusionThis study concludes as rs7932837 polymorphism in the HHEX gene showed positive association with recessive model and future studies recommend to carry out with large number of sample size with additional polymorphisms in HHEX gene.     

Association of ARHGEF11 R1467H polymorphism with risk for type 2 diabetes mellitus and insulin resistance in Chinese population

The human Rho guanine nucleotide exchange factor 11 (ARHGEF11), located on chromosome 1q21, is an activator of Rho GTPases involved in G protein signaling pathway known to regulate insulin secretion and action. The aim of our study was to evaluate the relationship between the previously reported R1467H G/A variant in ARHGEF11 and risk of type 2 diabetes mellitus (T2DM) and insulin resistance as well as metabolic traits in a Chinese population. We genotyped R1467H G/A polymorphism in 311 patients with T2DM and 328 control subjects in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol and DNA sequencing methods. The genotype and allele distributions of the R1467H G/A polymorphism were significantly different between the T2DM group and the normal control group (P = 0.024, 0.018, respectively) and we also found that the A allele carriers (GA + AA genotype) had markedly higher risk of T2DM as compared with the wild-type GG genotype after adjustment for gender, age, and BMI (OR = 1.578, 95% CI 1.126–2.212, P = 0.008). Moreover, in the T2DM group the A allele carriers had higher FPG, FINS, and HOMA-IR than that of the GG homozygote (P = 0.015, 0.029, and 0.007, respectively). FPG and HOMA-IR levels were also significantly increased from A allele carriers to GG homozygote in the control group (P = 0.017, 0.012, respectively). Our investigation suggests that the R1467H polymorphism of ARHGEF11 gene may contribute to susceptibility to T2DM and insulin resistance in a Chinese population.     

Association of SNP rs6903956 on chromosome 6p24.1 with angiographical characteristics of coronary atherosclerosis in a chinese population

Objective

To explore the association between rs6903956 and severity of coronary artery disease (CAD) in a Chinese population.

Methods

A cohort of 1075 consecutive patients who underwent coronary arteriography for suspected or known coronary atherosclerosis was enrolled in our study. Coronary atherosclerosis severity was defined by Gensini''s Score System and counts of diseased vessels.

Results

Gensini score frequencies and counts of diseased vessels differed among GG, AG, AA genotype groups at the rs6903956 locus (p = 0.025 for Gensini score frequencies vs. p = 0.024 for counts of diseased vessels, respectively). A univariate logistic regression analysis revealed that the genotype distribution of this SNP was associated significantly with angiographical characteristics of coronary atherosclerosis risk (p = 0.030, odds ratio (OR) = 1.444, 95% confidence interval (CI) = 1.036∼2.013 for AG vs. GG; p = 0.021, OR = 5.896, 95% CI = 1.299∼26.750 for AA vs. GG and p = 0.007, OR = 1.564, 95% CI = 1.132∼2.162 for combined (AG+AA) vs. GG). A multivariate logistic regression analysis indicated that the genotype distribution of the rs6903956 polymorphism be associated significantly with the angiographical characteristics of coronary atherosclerosis risk (p = 0.004, OR = 1.578, 95% CI = 1.155∼2.154 for GG vs. AG vs. AA; p = 0.013, OR = 1.541, 95% CI = 1.097∼2.163 for GG vs. GA+ AA). A stratification analysis revealed that male subjects and smoking subjects had a higher frequency of the rs6903956 heterozygous mutant among higher Gensini score subjects than among lower Gensini score subjects (p = 0.023, OR = 1.579, 95% CI = 1.064∼2.344 for male subgroup; p = 0.005, OR = 2.075, 95% CI = 1.249∼3.448 for smoking subgroup).

Conclusions

Allele A is a risk factor for CAD and the G-to-A allele substitution may underlie the association between rs6903956 and CAD.     

ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population

Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions between environmental factors and certain genetic factors. Genetic variants in the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been associated with abnormalities of serum lipid levels of high-density lipoprotein (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases, and this condition has been considered to be involved in the mechanism of insulin resistance (IR). Therefore, we investigated possible association between ABCA1 C69T gene polymorphism and T2DM in a Saudi population. This study was carried out with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. We observed that the frequency of the T allele of the ABCA1 C69T gene was significantly higher in healthy subjects compared to T2DM patients (0.28 vs 0.45; p<0.0001; OR (95% CI) = 0.4624 (0.3732–0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.     

Study on TFF1 and PALB2 gene variants associated with gastric carcinoma risk in the Chinese Han population

ObjectiveGastric carcinoma (GC) has received extensive attention due to its complex pathogenesis. Studies have shown that the expression of Trefoil factor 1 (TFF1) and Partner and localiser of BRCA2 (PALB2) genes promotes the occurrence of GC. Therefore, we investigated whether TFF1 and PALB2 gene polymorphisms are associated with GC risk in the Chinese Han population.MethodsA total of 509 GC cases and 505 controls were recruited, and single nucleotide polymorphisms (SNPs) of TFF1 and PALB2 in these subjects were genotyped. The association between each candidate polymorphism and GC risk was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The visualization of gene-gene interactions and functional enrichment analysis were then performed using Cytoscape software and the R package “cluster profile”.ResultsThe TFF1 rs2156310 polymorphism significantly reduced the predisposition to GC in people under 60 years of age (AA vs. AG - GG, OR = 0.58, 95% CI = 0.35–0.97, p = 0.036). The gender-stratified analysis found that PALB2 rs513313 was significantly associated with the risk of GC in males (CT vs. TT, OR = 1.51, 95% CI = 1.06–2.15, p = 0.022). Besides, PALB2 rs249954 significantly reduced the susceptibility to GC in females (AA vs GG, OR = 0.42, 95% CI = 0.19–0.94, p = 0.034).ConclusionOur results revealed that TFF1 and PALB2 gene polymorphisms were correlated with the genetic susceptibility to GC, providing certain data support for researchers to further study the mechanism of GC.     

Variants of NLRP3 gene are associated with insulin resistance in Chinese Han population with type-2 diabetes

Aims

Nod like receptor pyrin domain containing 3 (NLRP3) is the best characterized member of nod like receptor family. Recent studies suggest that NLRP3 plays a crucial role in the pathogenesis of type-2 diabetes (T2DM), and variants in NLRP3 affect its mRNA stability and expression. Therefore, we hypothesize that the variants in NLRP3 gene may contribute to T2DM susceptibility. The aim of this study is to evaluate the association of NLRP3 SNPs with T2DM in Chinese Han patients.

Methods

Two common variants in NLRP3 gene, rs10754558 and rs4612666, were detected using the polymerase chain reaction–restriction fragment length polymorphism procedure in 952 unrelated T2DM patients and 871 healthy controls. All participants were unrelated Chinese Hans.

Results

The GG genotype and G allele frequencies of rs10754558 were significantly higher in T2DM patients than those in controls (for GG genotype, 19.6% vs. 14.5%, p = 0.019; for G allele, 43.9% vs. 39.8%, p = 0.013). The GG genotype of rs10754558 was significantly associated with higher LDL-C levels and more prone to insulin resistance, as evaluated by HOMA-IR or QUICK indexes.

Conclusions

The variant (rs10754558) in NLRP3 is related to insulin resistance and increased risk of T2DM in Chinese Han population.     

Association of chemotactic chemokine ligand 5 rs2107538 polymorphism with tuberculosis susceptibility: A meta-analysis

A meta-analysis was carried out in this study by summarizing relevant research to evaluate the relationship between rs2107538 polymorphism in the chemotactic chemokine ligand 5 (CCL5) gene and tuberculosis (TB) susceptibility. Published studies were retrieved from PubMed, Embase, and CNKI databases using the keywords ‘CCL5’, ‘TB’, and ‘polymorphism’. Nine studies involving 2584 patients with TB and 2265 controls were included in the current meta-analysis. The combined results suggested that the CCL5 rs2107538 polymorphism was correlated with TB susceptibility (recessive model: OR = 1.45, 95% CI = 1.02–2.07). Subgroup analysis according to race indicated that such correlation could be detected in Caucasians (CT versus CC: OR = 1.53, 95% CI = 1.20–1.95; dominant model: OR = 1.58, 95% CI = 1.25–1.99), but not in East Asian, South Asian, and South African populations. In conclusion, the results of our meta-analysis suggest that CCL5 rs2107538 polymorphism might contribute to the risk of TB, especially in Caucasians. Well-designed studies with more subjects will be required for further validation of these results.     

Interleukin-10 ?592C/A, ?819C/T and ?1082A/G Polymorphisms with Risk of Type 2 Diabetes Mellitus: A HuGE Review and Meta-analysis

Background

Several studies have been conducted in recent years to evaluate the risk of type 2 diabetes mellitus (T2DM) and polymorphisms of interleukin (IL)-10. However, the results remain conflicting rather than conclusive. This meta-analysis aimed to summarize the current evidence from case-control studies that evaluated this association.

Methods

We carried out a search in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) database for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association.

Results

10 studies were included in our meta-analysis and systemic review. Our meta-analysis indicated that IL-10 −1082A/G polymorphism was associated with the risk of T2DM (GA vs. AA: OR = 1.21, 95% CI = 1.03–1.14; GA/GG vs. AA: OR = 1.22, 95% CI = 1.05–1.41), whereas there was no association between IL-10 −592C/A (CC/CA vs. AA: OR = 1.07, 95% CI = 0.59–1.93) or -819C/T (CC/CT vs. TT: OR = 0.93, 95% CI = 0.49–1.75) polymorphism and T2DM risk was found in our study.

Conclusions

This meta-analysis provides strong evidence that IL-10 −1082A/G polymorphism associated with risk of T2DM. However, no association of the IL-10 −592C/A or −819C/T polymorphism with T2DM risk was found. Additional well-designed large studies were required for the validation of our results.     

Adiponectin and peroxisome proliferator-activated receptor-γ gene polymorphisms and gene-gene interactions with type 2 diabetes

Aims

To investigate whether gene polymorphisms of both adiponectin and peroxisome proliferator-activated receptor gamma (PPARγ) influence type 2 diabetes mellitus (T2DM) respectively in the Han people of the Wenzhou region of China and whether the interaction of gene polymorphism between adiponectin and PPARγ influences T2DM in the same subjects.

Main methods

This study included 198 patients with T2DM and 255 healthy individuals. Polymerase chain reaction–restriction fragment length polymorphism analyses were used to detect single nucleotide polymorphisms (SNPs). Logistic regression and multifactor dimensionality reduction (MDR) methods were used to analyze gene–gene interactions.

Key findings

The frequency distribution of adiponectin SNP11377 was not different (p = 0.792), but the frequency of CC, CG and GG genotypes showed the difference between two groups (T2DM: 57.1%, 33.3%, and 9.6%; control: 53.7%, 41.6%, and 4.7%, respectively; p = 0.047). Adiponectin SNP45, SNP276 and PPAR γ SNPp12a were equally distributed between the two groups (p = 0.586, 0.119, 0.437, respectively), and there were no significant differences in genotype frequencies between the two groups (p = 0.751, 0.144, 0.479, respectively). Linkage disequilibrium existed between SNP11377 and SNP45 (p < 0.001) and SNP45 and SNP276 (p < 0.001). Haplotype analyses showed no significant differences between the T2DM and control groups. According to the logistic regression and MDR gene–gene interaction analyses, SNP11377GG and SNP276GT interactions increased the risk of T2DM (odds ratio = 6.984, p = 0.012).

Significance

Adiponectin SNP11377 and SNP276 gene–gene interactions are associated with the increased risk of T2DM in this population.     

The 223A>G polymorphism of the leptin receptor gene is associated with macroangiopathy in type 2 diabetes mellitus

To determine whether leptin receptor (LEPR) 223A>G polymorphism has an effect on the plasma leptin levels and the macroangiopathic complications in type 2 diabetes mellitus (T2DM). The genotypes and allelic frequencies of the LEPR 223A>G were examined with polymerase chain reaction and restriction fragment length polymorphism in 301 patients with T2DM and 172 unrelated healthy subjects. The plasma concentrations of leptin were determined in all subjects. The mean plasma leptin levels in the T2DM group were significantly higher than that of controls and the plasma levels of leptin were higher in diabetic patients with macroangiopathy than in patients without macroangiopathy (P < 0.05). The genotype (GG, AG and AA) distribution of 223A>G polymorphism was 58.3, 32.5, and 9.2% in diabetic patients with macroangiopathy, 75.3, 22.1, and 2.6% in patients without macroangiopathy, and 70.3, 27.5, 2.2% in controls respectively, a significant difference was found between diabetic patients with and without macroangiopathy (P < 0.05). The frequency of the allele A was higher in patients with macroangiopathy than in patients without macroangiopathy (25.6 vs. 16.3%; P < 0.05). Moreover, the plasma leptin levels were markedly higher in patients with AA genotype than those with AG or GG genotype in patients with macroangiopathy (P < 0.05). The LEPR 223A>G gene polymorphism associated with a predisposition to increased plasma leptin levels could constitute a useful predictive marker for diabetic macroangiopathy.     

Diabetes Status and Race are Associated With Cardiovascular Risk Markers in Obese Adolescents

ObjectiveThe objective of this study was to evaluate differences in cardiovascular disease (CVD) risk markers in obese adolescents based on diabetes status and race in order to improve risk-reduction intervention strategies.MethodsThis was a retrospective, cross-sectional study of obese adolescents, age 10 to 21 years, who were evaluated at Children’s of Alabama between 2000 and 2012. Subjects were classified by glycated hemoglobin (HbA_1c) as having normoglycemia, prediabetes, or type 2 diabetes mellitus (T2DM).ResultsThere were a total of 491 African American (AA) or Caucasian American (CA) subjects. Body mass index was not different between HbA_1c and racial groups. Compared to subjects with normoglycemia or prediabetes, subjects with T2DM had higher levels of total cholesterol (TC) (178.6 ± 43.8 mg/dL vs. 161.5 ± 32.5 mg/dL vs. 162.4 ± 30.6 mg/dL; P < .0001) and low-density-lipoprotein cholesterol (107.4 ± 39.2 mg/dL vs. 97.0 ± 31.0 mg/dL vs. 97.5 ± 26.9 mg/dL; P = .0073). Compared with AA subjects, CA subjects had lower high-density-lipoprotein cholesterol (HDL-C) levels (40.4 ± 10.4 mg/dL vs. 44.3 ± 11.9 mg/dL; P = .0005) and higher non-HDL-C levels (129.6 ± 36.2 mg/dL vs. 122.5 ± 37.5 mg/dL; P = .0490). Of the characteristics studied, HbA_1c had the most significant positive association with dyslipidemia and was strongly correlated with both TC (β, 4.21; P < .0001) and non-HDL-C (β, 4.3; P < .0001).ConclusionObese adolescents with T2DM have more abnormal lipoprotein profiles than those with normoglycemia or prediabetes. Obese CA adolescents have more abnormal lipids than obese AA adolescents. HbA_1c was the characteristic most highly associated with abnormal lipoprotein profiles in our subjects. Our results show that CVD risk markers in obese adolescents vary by race and HbA_1c concentration. (Endocr Pract. 2015;21:165-173)     

Cyclin D1 G870A polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case–control study

Background: A common G to A polymorphism (G870A) in the splice donor region of exon 4 of cyclin D1 (CCND1) gene generates two mRNAs (cyclin D1a and D1b) through an alternative splicing at the site of this polymorphism. Cyclin D1a and b proteins differ in their COOH-terminus, a region involved in protein degradation. We examined the association between this CCDN1 genotype and the susceptibility to hepatocellular carcinoma (HCC) in a Turkish population. Methods: The genotype frequency of this polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. Hospital-based case–control study was designed consisting of 160 diagnosis subjects with hepatocellular carcinoma and 160 cancer-free control subjects matched on age, gender, smoking and alcohol status. Results: The allele frequencies of case subjects (A, 0.55; G, 0.45) were significantly different from those of control subjects (A, 0.42; G, 0.58) (p = 0.002). The odds ratios (ORs) for the CCND1 870 GA and AA genotypes when compared with the GG genotypes were 1.39 (95% confidence interval [CI] 0.82–2.36, p = 0.22) and 2.52 (95% CI 1.38–4.62, p = 0.003) respectively. The presence of at least one CCND1 870A allele was associated with increased risk for HCC (OR, 1.73; 95% CI, 1.06–2.82, p = 0.03). When combining the GG and GA genotypes as a reference genotype, we found that the OR for the AA genotype was 2.06 (95% CI 1.24–3.44, p = 0.006). Conclusion: Our results suggest that the CCND1 G870A single nucleotide polymorphism is associated with an increased risk of HCC in our Turkish population.     

Correlation between polymorphisms in IGF2/H19 gene locus and epithelial ovarian cancer risk in Chinese population

To investigate the association between SNPs in human IGF2/H19 gene locus and epithelial ovarian cancer (EOC) risk, we performed a case-control study in 422 individuals (219 EOC patients and 203 cancer-free controls). Four SNPs (rs2525885, rs2839698, rs3741206, rs3741219) were found to be related with EOC risk. Specifically, the minor allele C of rs2525885 and allele A of rs2839698 was associated with elevated EOC genetic susceptibility under both dominant and recessive models (TC + CC vs TT: adjusted OR: 1.61, P = .031; CC vs TT + TC: adjusted OR: 4.87, P = .014; GA + AA vs GG: adjusted OR: 1.63, P = .023; AA vs GG + GA: adjusted OR: 2.43, P = .007). For rs3741206, the genotype TC + CC was associated with a significant decrease in EOC risk with the TT genotype as reference in a dominant genetic model (adjusted OR: 0.44, P = .003), while for rs3741219, genotype AA was associated with a 59% decrease in EOC risk only in the recessive model (adjusted OR: 0.41, P = .038). In the stratified analysis, an increased risk associated with the variant genotypes was observed in only subjects aged >47 years for rs2525885 (adjusted OR = 2.04, P = .024), rs2839698 (adjusted OR = 2.50, P = .047) and rs3741206 (adjusted OR = 0.37, P = .009), respectively. What's more, the TC + CC genotype of rs2525885 was significantly associated with advanced FIGO stage (III vs II, adjusted OR = 2.73, P = .040).     

The Effect of MUC1 rs4072037 Functional Polymorphism on Cancer Susceptibility: Evidence from Published Studies

Genome-wide association studies have identified a susceptibility variation MUC1 rs4072037 for gastric cancer in Chinese population. Subsequent case-control studies have reported this association in other populations. However, the results remain controversial and ambiguous. The aim of this study is to provide a precise quantification for the association between MUC1 rs4072037 variation and the risk of cancer. We performed pooled analysis of 10 case-control designed studies including 4,220 cases and 6,384 controls. Odds ratios (OR) and 95% confidence interval (95%CI) were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity and cancer types. All statistical analyses were performed by Manager 5.0 and Stata 12.0 software. Overall, the MUC1 rs4072037 polymorphism was associated with risk of cancer in all genetic models (G vs A: OR = 0.71, 95%CI: 0.63–0.80, p<0.01; GA vs AA: OR = 0.61, 95%CI:0.55–0.67, p<0.01; GG vs AA: OR = 0.58, 95%CI: 0.47–0.71, p<0.01; AG+AA vs GG: OR = 0.60, 95%CI: 0.55–0.60, p<0.01; GG vs AG+AA: OR = 0.70, 95%CI: 0.58–0.85, p<0.01). Further, subgroup analysis based on ethnicity suggested MUC1 rs4072037 polymorphism had a subtly reduced cancer risk among Asian population, and stratified analysis by cancer types showed significantly decreased risk of gastric cancer in all genetic models. In conclusion, MUC1 rs4072037 polymorphism may be used as potential biomarker for cancer susceptibility particularly for gastric cancer and for Asian population.     

MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population

Background: The mouse double minute 2 (MDM2) gene represents one of the central nodes in the p53 pathway. A naturally occurring T/G single nucleotide polymorphism (SNP) in the intronic promoter of MDM2, SNP309 (rs2279744), was shown to influence MDM2 expression and p53 activity. SNP in the promoter region of MDM2 gene has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. In this study, we aim to evaluate the association of SNP309 with the risk of hepatocellular carcinoma (HCC) development among Turkish population. Methods: MDM2 SNP309 polymorphism was investigated in 110 confirmed subjects with HCC and 110 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay. Results: The allele frequencies of case subjects (T, 0.48; G, 0.52) were significantly different from those of control subjects (T, 0.65; G, 0.35) (p = 0.003). The proportion of GG genotype of the SNP309 in patients with HCC (26%) was significantly higher than that in patients without HCC (14%). We observed that compared with the TT genotype, the genotypes containing G allele [TG (OR, 2.19; 95% CI, 1.18–4.07; p = 0.013) or GG (OR, 3.63; 95% CI, 1.65–8.00; p = 0.001)] were associated with significant increased susceptibility to HCC. Conclusion: Our findings suggest that the MDM2 promoter SNP309 G allele is associated with presence of HCC in Turkish population.     

Independent case-control study in KCNJ11 gene polymorphism with Type 2 diabetes Mellitus

BackgroundType 2 Diabetes Mellitus (T2DM) is the most common form of diabetes in the aging population. This chronic metabolic disorder has discovered many candidate genes, and KCNJ11 was one of the genes associated with insulin secretion pathways mediated by potassium channels. There have been limited studies on the rs5210 polymorphism in T2DM patients, and none of them have been conducted in Saudi Arabia.AimThe aim of this study is to investigate at genotyping levels of rs5210 polymorphism in the KCNJ11 gene in older population with T2DM in the Saudi Population.MethodsBased on the sample size design, this case-control study included 102 T2DM cases and 102 controls. Using the PCR-RFLP assay, 204 patients extracted DNA was genotyped for the rs5210 polymorphism. SPSS software was used for statistical analysis, including t-tests, HWE, genotyping, and multiple logistic regression analysis.ResultsThe t-tests performed on T2DM cases and controls revealed a significant association in age, weight, BMI, FBG, Hb1Ac, SBP, DBP, HDLC, TC, and TG parameters (p < 0.05). HWE analysis found to be in consistent with rs5210 polymorphism. Allelic association was found in the rs5210 polymorphism (OR-1.64 [95 %CI: 1.08–2.49]; p = 0.01); however, no association (p > 0.05) was observed in the multivariate logistic regression assessment performed in this study.ConclusionThese results indicate that the rs5210 polymorphism was primarily associated with allele frequencies, which could be attributable to the small sample size. Large sample size studies will be required to determine whether KCNJ11 gene polymorphisms may be required as a risk marker for T2DM in the Saudi population.     

Association study of the β2-adrenergic receptor gene polymorphisms and hypertension in the Northern Han Chinese

Background

The β2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population.

Methodology/Principal Findings

This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059–1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121–1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059–2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056–1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258–2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk.

Conclusions/Significances

We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.