CC Homozygote Genotype Research Articles

Association of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants and type 1 diabetes mellitus.

Type I diabetes mellitus (T1DM) is a significant health challenge, especially for children, owing to its chronic autoimmune nature. Although the exact etiology of T1DM remains elusive, the interplay of genetic predisposition, immune responses, and environmental factors are postulated. Genetic factors control immune reactivity against β-cells. Given the pivotal roles of CIITA and CLEC2D genes in modulating a variety of immune pathologies, we hypothesized that genetic variations in CIITA and CLEC2D genes may impact T1DM disease predisposition. This study was designed to explore the association between gene polymorphisms in CIITA (rs8048002) and CLEC2D (rs2114870) and type 1 diabetes (T1DM), with a focus on analyzing the functional consequence of those gene variants. The study enlisted 178 healthy controls and 148 individuals with type 1 diabetes (T1DM) from Suez Canal University Hospital. Genotyping for CIITA and CLEC2D was done using allelic-discrimination polymerase chain reaction (PCR). Levels of glycated hemoglobin (HbA1c) and lipid profiles were determined through automated analyzer, while fasting blood glucose and insulin serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RegulomeDB was used to examine the regulatory functions of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants. Analysis of the genotype distribution of the CIITA rs8048002 polymorphism revealed a significantly higher prevalence of the rare C allele in T1DM patients compared to the control group (OR = 1.77; P = 0.001). Both the CIITA rs8048002 heterozygote TC genotype (OR = 1.93; P = 0.005) and the rare homozygote CC genotype (OR = 3.62; P = 0.006) were significantly more frequent in children with T1DM when compared to the control group. Conversely, the rare A allele of CLEC2D rs2114870 was found to be significantly less frequent in T1DM children relative to the control group (OR = 0.58; P = 0.002). The heterozygote GA genotype (OR = 0.61; P = 0.033) and the rare homozygote AA genotype (OR = 0.25; P = 0.004) were also significantly less frequent in T1DM patients compared to the control group. Both CIITA (rs8048002) and CLEC2D (rs2114870) gene variants were predicted to have regulatory functions, indicated by a RegulomeDB score of (1f) for each. The rare C allele of CIITA rs8048002 genetic variant was associated with an increased risk of developing T1DM, while the less common A allele of CLEC2D rs2114870 was associated with a reduced risk of T1DM. The online version contains supplementary material available at 10.1007/s40200-024-01402-w.

The Aquaporin 3 Polymorphism (rs17553719) Is Associated with Sepsis Survival and Correlated with IL-33 Secretion.

Sepsis is a common life-threatening disease caused by dysregulated immune response and metabolic acidosis which lead to organ failure. An abnormal expression of aquaporins plays an important role in organ failure. Additionally, genetic variants in aquaporins impact on the outcome in sepsis. Thus, we investigated the polymorphism (rs17553719) and expression of aquaporin-3 (AQP3) and correlated these measurements with the survival of sepsis patients. Accordingly, we collected blood samples on several days (plus clinical data) from 265 sepsis patients who stayed in different ICUs in Germany. Serum plasma, DNA, and RNA were then separated to detect the promotor genotypes of AQP3 mRNA expression of AQP3 and several cytokines. The results showed that the homozygote CC genotype exhibited a significant decrease in 30-day survival (38.9%) compared to the CT (66.15%) and TT genotypes (76.3%) (p = 0.003). Moreover, AQP3 mRNA expression was significantly higher and nearly doubled in the CC compared to the CT (p = 0.0044) and TT genotypes (p = 0.018) on the day of study inclusion. This was accompanied by an increased IL-33 concentration in the CC genotype (day 0: p = 0.0026 and day 3: p = 0.008). In summary, the C allele of the AQP3 polymorphism (rs17553719) shows an association with increased AQP3 expression and IL-33 concentration accompanied by decreased survival in patients with sepsis.

Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients

BackgroundThe genetic architecture of rheumatoid arthritis (RA) and osteoarthritis (OA) are still unclear. Although RA and OA have quite different causes, they share synovial inflammation, risk factors, and some disease-associated genes, including the integrin subunit β2 (ITGB2)/CD18 gene involved in extracellular matrix interactions and immune cell signaling. However, the functional role of ITGB2 genetic variants, its circulating expression pattern, and their clinical usefulness in RA and OA remain unexplored. Our study appraised the association of ITGB2 rs2070946 single nucleotide polymorphism with the vulnerability to RA and OA and its influence on ITGB2 mRNA expression, along with the potential of serum ITGB2 expression in RA and OA diagnosis.MethodsThis study included 70 RA patients, 70 primary OA patients, and 60 healthy volunteers. Genotyping and gene expression analysis were performed using qPCR. Bioinformatics analysis was employed to construct the protein-protein interaction (PPI) network of ITGB2.ResultsSerum ITGB2 mRNA expression was upregulated in both RA and OA compared to healthy controls. ITGB2 rs2070946 was associated with escalating risk of both diseases. RA patients harboring the rs2070946 CC or TC + CC genotypes had higher serum ITGB2 expression than the TT genotype carriers. Likewise, OA patients having the minor homozygote CC genotype had higher serum ITGB2 expression than those carrying the TT, TC or TT + TC genotypes. Serum ITGB2 expression showed profound diagnostic potential for RA and OA in receiver-operating characteristic analysis. In RA, serum ITGB2 expression positively correlated with rheumatoid factor and disease activity score 28 (DAS28). The ITGB2-PPI network enriched in cell-cell adhesion, ICAM-3 receptor activity, T-cell activation, leukocyte adhesion, complement binding, and NF-κB, tumor necrosis factor, and interleukin signaling pathways.ConclusionThese findings embrace the impact of ITGB2 rs2070946 as a novel genetic biomarker of both RA and OA, which could alter the ITGB2 expression. Serum ITGB2 expression could aid in timely diagnosis of RA and OA.

Association of GIPR gene variant on the risk of type 2 diabetes mellitus: A case-control study

BackgroundType 2 diabetes mellitus (T2DM), as a worldwide health challenge, is a multifactorial disease that environmental and genetic factors contribute to its pathogenicity. Gastric Inhibitory Polypeptide Receptor (GIPR) is a G-pro receptor that controls the gut hormones release and insulin secretion. The current study aimed to investigate the role of the GIPR rs1800437 gene variant in T2DM susceptibility. Material and methodsA total of 108 confirmed T2DM patients and 100 normal controls were recruited in the study. The GIPR rs1800437 genotypes were determined by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. ResultsA significant difference was found in genotypes (CC, CG, and GG) frequency of the GIPR rs1800437 variant between T2DM and control groups (P = 0.02). The homozygote CC genotype of the variant significantly decreased the odds ratio (OR) of diabetes mellitus risk, approximately 50 %, in comparison with the heterozygous GC genotype. The frequency of the C allele among cases was considerably lower than controls (P = 0.002, OR = 0.51, CI = 0.33–0.79). ConclusionThe findings of the study show enough evidence that there is a significant association between the rs1800437 GIPR genetic variant and the risk of T2DM.

Ninjurin 2 rs118050317 gene polymorphism and endometrial cancer risk

BackgroundEndometrial cancer is one of the most common female reproductive system tumors. Ninjurin2 (NINJ2) is a new adhesion factor. As a vascular susceptibility gene, it is highly expressed in other cancers and promotes the growth of cancer cells. We conducted an association analysis between NINJ2 gene polymorphism and endometrial cancer risk.MethodsFive SNPs rs118050317, rs75750647, rs7307242, rs10849390 and rs11610368 of NINJ2 gene were genotyped in 351 endometrial cancer patients and 344 healthy controls. The clinical index difference between cases and controls were tested by one-way analysis of variance. The allele and genotype frequency of cases and controls were been compared by Chi square test. The odds ratios (OR) with 95% confidence interval (95% CI) were examined by logistic regression analysis.ResultsThe SNP rs118050317 mutant allele C and homozygote CC genotype were significant increased the endometrial cancer risk (OR 1.46, 95% CI 1.04–2.06, p = 0.028; OR 8.43, 95% CI 1.05–67.89, p = 0.045). In the clinical index analysis, there were significant higher quantities of CEA, CA125 and AFP in cases serum than controls.ConclusionThe NINJ2 gene polymorphism loci rs118050317 mutant allele C was associated with an increased risk of endometrial cancer. CEA, CA125 and AFP quantities were significant higher in endometrial cancer patients.

Association between interleukin 6 gene polymorphism and human papilloma virus infection in Oral Squamous Cell Carcinoma patients

Background: Both HPV and IL 6 gene polymorphism have independently proven their association with OSCC. And we assume that the positivity of both HPV and IL 6 in a patient with OSCC would raise the threshold of patient towards the aggressiveness of the disease.So the aim was to find an association between Human Papilloma Virus and IL 6 gene polymorphism in Oral Squamous Cell Carcinoma patients. Methods and materials: Methodology: This cross-sectional study was conducted at Ziauddin Hospital, Karachi, between Jan 2014 to May 2015. And of consisted a total of 140 oral squamous cell carcinoma patients of 18 y and above (104 males and 36 females). Detailed questionnaire followed by sample collection from each patient was done. These samples were analyzed by polymerase chain reaction for human papilloma virus and IL 6 gene polymorphism was analyzed through restriction fragment length polymorphism. Results: Mean age of the patients was 43.5 ± 11.84 y (range 31–40 y). Most of the patients (45; 32.1%) belonged to the Urdu speaking ethnic group. Pan (87; 62.1%) and Gutka (82; 58.6%) were used by most of the patients. (17;12.1%) patients had history of systemic disease (e.g hypertension, diabetes). And (3021.4%) patients had a positive family history of OSCC. The most common site of OSCC was buccal mucosa (86; 61.4%) in these patients. Majority of the patients (77; 55%) had histologically moderately differentiated OSCC, and more than half of these patients (78; 55.7%) had Group B (stage III & IV) of OSCC. (12;8.6%) out of 140 samples tested positive for human papilloma virus gene and the following pattern was observed for IL 6 gene polymorphism, GG: (46.4%), GC (39.3%), CC (14.3%). A positive association was observed for Group B (stages III & IV) of oral squamous cell carcinoma with IL 6 genotypes: GC heterozygote (OR = 3.819, 95% CI = 1.782-8.183, p = 0.001) and CC homozygote (OR = 6.833, 95% CI = 2.046-22.822, p = 0.002), and also a strong positive association was found between human papilloma virus and CC homozygote genotype (OR = 21.333, 95% CI = 2.318-196.311, p = 0.007). Conclusion: Human papilloma virus association with IL 6 gene polymorphism in oral squamous cell carcinoma patients suggests rapid and aggressive progress of oral carcinogenesis.

Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker

Genetic polymorphisms of NEIL1 and NEIL2 maybe change protein function, and increased carcinogenesis. In this study, seven NEIL1 SNPs and three NEIL2 SNPs were selected. 400 CSCCs, 400 CIN III, and 1200 normal healthy controls were genotyped by mismatch amplification PCR. mRNA and protein expression of NEIL2 was measured in 92 freshly-obtained CSCC tumor tissues. The association between homozygote CC genotype of NEIL2 rs804270 with susceptible risk was gradually increased in CIN III (OR = 1.44) and CSCC (OR = 2.22). Carriers of C-allele (GC + CC) at rs804270 had a high risk of CSCC (OR = 1.46). The heterozygote GT genotype of rs8191664 was also closely related to the higher risk of CINIII (OR = 1.59) and CSCC (OR = 2.54). Carriers of T-allele (GT + TT) at rs8191664 had a high risk for CIN III (OR = 1.55) and CSCC (OR = 2.34). The genotypes of NEIL2 rs804270 (G/C) and rs8191664 (G/T) that were related to the higher risk for CIN III were CC-GG (OR = 1.42) and CC-GT (OR = 2.07). More notably, there was a greater risk for CSCC with the GC-GT (OR = 1.91), CC-GG (OR = 1.67), and CC-GT (OR = 6.18) genotypes. NEIL2 mRNA expression in CSCCs with the rs804270-CC genotype was lower expression than those in CSCCs with the rs804270-GG and rs804270-GC genotypes. Similarly, NEIL2 protein expression was significantly decreased in CSCCs with the rs804270-CC genotype. In summary, the two genetic polymorphisms (rs804270 and rs8191664) of NEIL2 gene were significantly associated to the increased susceptibility of CIN III or CSCC. This increased susceptibility maybe due to altered NEIL2 repair activity through altered protein expression, or changed structure of the functional domain. The genotypes of GC-GT, CC-GG, and CC-GT of rs804270 and rs8191664 of NEIL2 gene could act as a genetic predictive biomarker of susceptibility to CIN III and CSCC.

Association between ADORA2A gene polymorphisms and schizophrenia in the North Chinese Han population.

BackgroundA large number of studies have shown a close relationship between ADORA2A and the pathological mechanism of schizophrenia. However, to our knowledge, there has been no studies examining the association between the ADORA2A gene and schizophrenia in Chinese Han population.PurposeThe objective of this study was to examine the relationship between adenosine A2A receptor (ADORA2A) single nucleotide polymorphisms and schizophrenia in the North Chinese Han population.Patients and methodsWe detected ADORA2A single nucleotide polymorphisms (SNPs) using polymerase chain reaction-restriction fragment length polymorphism analyses and summarized our results using SPSS statistical software and Haploview in schizophrenia case group (n=398) and healthy control group (n=535).ResultsThe frequency of the CC homozygote genotype of SNP rs2298383T/C were significantly higher in the case than the control group (p=0.005, OR=1.712, 95% CI=1.172–2.502). After linkage disequilibrium analysis, SNPs rs5996696A/C and rs2298383T/C displayed strong linkage disequilibrium. We found that the frequencies of haplotypes TA (χ2=6.268, p=0.0123) and CA (χ2=7.012, p=0.0081) were significantly higher in the case group than in the control group.ConclusionIn conclusion, SNPs in the ADORA2A gene may be associated with schizophrenia in the northern Chinese Han population.

Association of two polymorphisms rs3740199 and rs1871054 at ADAM12 with susceptibility of knee osteoarthritis: a systematic review and meta-analysis

Background: Osteoarthritis (OA) is the most common joint disease that mainly influences the knees, hips, hands and spine. However, the pathogenesis of knee OA remains poorly understood. A number of studies have explored the association between ADAM12 polymorphisms and the risk of knee OA in different populations. We aimed to systematically review those observational studies, taking into account the variable quality of studies. Methods: We carried out a systematic review and meta-analysis of these studies based on ADAM12 rs3740199 and rs1871054 genotypes. Four comparisons involving 2 Chinese, 1 Korean and 1 Thai population of 1,241 knee OA patients and 2,316 controls were included in our study. Results: For the SNP rs1871054, the C allele was associated with an increased risk of knee OA in terms of the frequency of allele comparison. For a dominant model of the C allele, the CT + CC genotypes were associated with the risk for knee OA. The CC homozygote genotype was also associated with increased susceptibility to knee OA. However, the ADAM12 rs3740199 polymorphism was suggested not to be related to knee OA susceptibility in all populations. Conclusions: The present results suggested that there existed a positive relationship between the ADAM12 rs1871054 polymorphisms with the susceptibility of knee OA, while the ADAM12 rs3740199 was not observed to be associated with the risk of knee OA.

Programmed death-1 polymorphisms is associated with risk of esophagogastric junction adenocarcinoma in the Chinese Han population: A case-control study involving 2,740 subjects.

Single nucleotide polymorphisms (SNPs) in Programmed cell death 1 (PD-1) gene may contribute to the development of cancer. In this study, we selected PD-1 rs10204525 T>C, rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms and designed a hospital-based case-control study to determine the potential relationship between these functional SNPs in PD-1 gene and esophagogastric junction adenocarcinoma (EGJA) risk. A total of 1,063 EGJA patients and 1,677 controls were enrolled from Eastern Chinese Han population. SNPscanTMgenotyping assay was used to analyze the genotyping of PD-1 polymorphisms. We found that PD-1 rs7421861 A>G polymorphism was associated with the development of EGJA. However, PD-1 rs2227982 A>G polymorphism was a protective factor for EGJA. In addition, PD-1 rs36084323 CC homozygote genotype might be associated with a borderline decreased risk of EGJA. In a subgroup analysis, a decreased risk of EGJA in never drinking and never smoking groups was identified. Haplotype comparison analysis suggested that PD-1 Trs10204525Grs2227982C36084323Ars7421861 haplotype significantly decreased the risk of EGJA. However, Trs10204525Grs2227982C36084323Grs7421861 haplotype in PD-1 gene may confer risk to EGJA. In conclusion, our study highlights rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms and haplotypes in PD-1 gene, especially within the intron region, are significantly associated with the risk of EGJA. Further case-control studies with larger sample size and detailed gene-environmental data to replicate these findings in different populations are needed to validate our conclusion.

Hsa-mir-499 rs3746444 T/C Polymorphism is Associated with Increased Risk of Coronary Artery Disease in a Chinese Population.

Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms hsa-mir-499 rs3746444 T/C, IRAK1 rs3027898 C/A and RANKL rs7984870 C/G might contribute to CAD susceptibility. We studied the association between the three polymorphisms and the risk of CAD in a Chinese population using 435 CAD patients and 480 controls. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to perform the genotyping, and the differences were analysed. When the hsa-mir-499 rs3746444 TT homozygote genotype was used as the reference group, the TC, CC or TC/CC genotypes were associated with a significantly increased risk of CAD [TC vs. TT: adjusted odds ratio (OR) 1.41, 95% confidence interval (CI) 1.02-1.94, p = 0.04; CC vs. TT: adjusted OR 3.14, 95% CI 1.77-5.56, p < 0.001; CC/TC vs. TT: adjusted OR 1.68, 95% CI 1.25-2.26, p < 0.001). In the recessive model, when the hsa-mir-499 rs3746444 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of CAD (adjusted OR 2.87, 95% CI 1.63-5.04, p < 0.001). Risk factors such as diabetes mellitus (DM), hypertension, smoking and low high-density ipoprotein cholesterol (HDL-c) were also associated with a significantly increased risk for CAD. Logistic regression analyses revealed that IRAK1 rs3027898 C/A and RANKL rs7984870 C/G polymorphisms were not associated with risk of CAD. These findings suggested that the functional polymorphism hsa-mir-499 rs3746444 T/C is associated with CAD susceptibility.

Association of interleukin-6 gene polymorphisms and circulating levels with keloid scars in a Chinese Han population.

The aim of the present study is to explore the effect of IL-6 gene polymorphisms on the development of keloid scar (KS) in the Chinese Han population. Genotyping of IL-6 was performed by the polymerase chain reaction (PCR), followed by restriction fragment length polymorphism assays (PCR-RFLP). Serum level of IL-6 was measured using enzyme-linked immunosorbent assay (ELISA). Results indicated that when the IL-6 -572 CC homozygote genotype was used as the reference group, the GG genotype was found to be associated with a significantly increased risk of KS (GG vs CC: OR = 2.097, 95%CI = 1.100-3.995, P = 0.025). When the IL-6 -572 C allele was used as the reference group, the G allele was found to be associated with significantly increased risk of KS (G vs C: OR = 1.317, 95%CI = 1.002-1.730, P = 0.048). Furthermore, we observed a marked increase in serum IL-6 levels in KS patients with GG genotypes when compared to KS patients harboring the CC genotype. In conclusion, our results suggest that IL-6 gene polymorphism was associated with keloid scars in the southeastern Chinese Han population.

Investigation of association between IL-8 serum levels and IL8 polymorphisms in Chinese patients with sepsis

ObjectiveTo assess the clinical relevance of IL8 gene polymorphisms in patients with sepsis and its association with systemic IL-8 levels. MethodsPCR and DNA sequencing were used to examine the polymorphism of IL8 in 152 patients with sepsis and in 199 healthy volunteers in China. The distribution frequencies of the genotype and allele were compared among different groups. The serum IL-8 was measured by ELISA and analyzed in relation to polymorphisms of IL8. ResultsThe homozygote TT genotype and T allele of rs4073 (genotype: p=0.01, allele: p=0.002), the homozygote CC genotype and C allele (genotype: p=0.03, allele: p=0.003) of rs2227306, homozygote AA genotype and A allele of re1126647 (genotype: p=0.01, allele: p=0.002) were associated with susceptibility to sepsis in males. Serum IL-8 levels were significantly increased in patients with sepsis but showed no correlation with IL8 rs4073, rs2227306 and rs1126647 polymorphisms. ConclusionsThe male population carrying the homozygote TT genotype and T allele of rs4073, the homozygote CC genotype and C allele of rs2227306 and homozygote AA genotype and A allele of rs1126647 are more susceptible to sepsis, suggesting there is a protective effect in females carrying these genotypes and alleles respectively. There was no association between rs4073, rs2227306 and rs1126647 polymorphisms and serum levels of IL-8 in patients with sepsis.

MiR-196a2 rs11614913 T>C Polymorphism is Associated with an Increased Risk of Tetralogy of Fallot in a Chinese Population.

MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNAs that act as post-transcriptional gene regulatory elements. MiRNA polymorphisms may be associated with susceptibility to congenital heart disease (CHD). The aim of this study was to evaluate the impact of miRNA single nucleotide polymorphisms (SNPs) on CHD susceptibility. We genotyped two functional SNPs, miR-196a2 rs11614913 and miR-146a rs2910164, in a case-control cohort of 173 Chinese patients with tetralogy of Fallot (TOF) and 207 non-CHD controls. When the miR-196a2 rs11614913 TT homozygote genotype was used as the reference group, the TC genotype was not associated with an increased risk of TOF. The CC genotype was associated with a borderline significantly increased risk for TOF. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of TOF (OR = 1.96, 95% CI = 1.18-3.25, p = 0.01). The miR-146a rs2910164 C>G polymorphism was not associated with developing TOF. Our findings suggested that the miR-196a2 rs11614913 T>C polymorphism may play a role in the development of TOF. Future larger studies that include populations of other ethnicities are required to confirm these findings. Congenital heart disease; MiRNA; Molecular epidemiology; Polymorphisms; Tetralogy of Fallot.

Methylenetetrahydrofolate reductase C667T polymorphism is associated with increased risk of coronary artery disease in a Chinese population.

Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) rs1801133 C/T, matrix metalloproteinases (MMPs)-2, tumour necrosis factor (TNF)-α, macrophage migration inhibitory factor (MIF) rs755622G/C and cyclin D1 (CCND1) rs678653G/C contribute to CAD susceptibility. We examined the association between the five polymorphisms and the risk of CAD in a Chinese population of 435 CAD patients and 480 controls. Genotyping was performed using matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI/TOF MS). When the MTHFR rs1801133 CC homozygote genotype was used as the reference group, the TT or CT/TT genotypes were associated with a significantly increased risk for CAD. The CT heterozygote genotype was not associated with the risk for CAD. Logistic regression analyses revealed that MMP-2 rs243865 C/T, TNF-α rs1800629 A/G, MIF rs755622G/C and CCND1 rs678653G/C polymorphisms were not associated with the risk of CAD. These findings suggest that the MTHFR rs1801133 C/T polymorphism is associated with CAD development. Future larger studies with other ethnic populations are required to confirm current findings.

TERT-CLPTM1L Rs401681 C&gt;T Polymorphism Was Associated with a Decreased Risk of Esophageal Cancer in a Chinese Population

BackgroundEsophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90 percent of esophageal cancers. Genetic factors probably play an important role in the ESCC carcinogenesis.MethodsWe conducted a hospital based case-control study to evaluate functional hTERT rs2736098 G>A and TERT-CLPTM1L rs401681 C>T single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction (LDR) method.ResultsWhen the TERT-CLPTM1L rs401681 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly decreased risk of ESCC (adjusted OR = 0.74, 95% CI = 0.58–0.94, p = 0.012); the CT/TT variants were associated with a 26% decreased risk of ESCC (adjusted OR = 0.74, 95% CI = 0.59–0.93, P = 0.009). The significantly decreased risk of ESCC associated with the TERT-CLPTM1L rs401681 C>T polymorphism was associated with male sex, young age (<63 years in our study) and alcohol consumption. No association between the hTERT rs2736098 G>A polymorphism and ESCC risk was observed.Conclusion TERT-CLPTM1L rs401681 CT and CT/TT genotypes were associated with decreased risk of ESCC, particularly among men, young patients and those reported to be drinkers. However, our results are preliminary conclusions. Larger studies with more rigorous study designs are required to confirm the current findings.

P21 rs3176352 G>C and p73 rs1801173 C>T polymorphisms are associated with an increased risk of esophageal cancer in a Chinese population.

ObjectiveEsophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Genetic factors might play an important role in esophageal squamous cell carcinoma (ESCC) carcinogenesis.Designs and MethodsTo evaluate the effect p21, p53, TP53BP1 and p73 single nucleotide polymorphisms (SNPs) on the risk of ESCC, we conducted a hospital based case–control study. A total of 629 ESCC cases and 686 controls were recruited. Their genotypes were determined using ligation detection reaction (LDR) method.ResultsWhen the p21 rs3176352 GG homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk of ESCC. When the p73 rs1801173 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly increased risk of ESCC. After Bonferroni correction, for p21 rs3176352 G>C, the p correct was still significant. For the other six SNPs, in all comparison models, no association between the polymorphisms and ESCC risk was observed.Conclusions p21 rs3176352 G>C and p73 rs1801173 C>T SNPs are associated with increased risk of ESCC. To confirm the current findings, additional, larger studies and tissue-specific biological characterization are required.

Association between miR-146aG&gt;C and miR-196a2C&gt;T polymorphisms and the risk of hepatocellular carcinoma in a Chinese population

MicroRNAs have been demonstrated to have a role in susceptibility and prognosis of various types of human cancer. We investigated the association between polymorphisms in miR-146aG>C, miR-196a2C>T, and miR-499A>G and hepatocellular carcinoma (HCC) risk and interaction with HCC and hepatitis B virus (HBV) infection. Two hundred sixty-six cases with HCC and 281 health controls were enrolled in the present study. Genotyping of the miR-146aG>C, miR-196a2C>T, and miR-499A>G genotypes was conducted by duplex polymerase chain reaction with the confronting two-pair primer (PCR-RFLP). Subjects with miR-146a GG and G allele had an increased risk of HCC compared with the homozygote CC genotype. Similarly, HCC patients carrying microRNA (miRNA)-196a2 computed tomography, TT, and T allele significantly decreased the risk of HCC relative to the CC genotype. Stratified analysis indicated that miR-196a2C>T polymorphism was associated with reduced risk of HBV-related HCC, but not in hepatitis C virus- and nonviral-related HCC cases. In conclusion, miR-146aG>C and miR-196a2C>T polymorphism are associated with risk of HCC patients in China, especially in patients with HBV infection. SNPs in miRNA sequences can be used as a diagnostic biomarker for HCC.

Human leukocyte antigen (HLA)-C polymorphisms are associated with a decreased risk of rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune rheumatological disease thought to have substantial genetic contributions. Several genetic factors involved in the susceptibility to psoriasis and psoriatic arthritis (PsA) have been identified with genome-wide association studies, including human leukocyte antigen (HLA)-C, junction adhesion molecule 2 (JAM2) and REL. Psoriasis and PsA may share many features in common with RA. We hypothesized that this polymorphism may contribute to RA susceptibility in a Chinese population. We studied HLA-C rs10484554 C/T, HLA-C rs12212594 T/C, HLA-C rs12191877 C/T, JAM2 rs2829866 A/T and REL rs702873 G/A polymorphisms in 520 patients with RA and 520 controls in a Chinese population. HLA-C rs12191877 C/T polymorphism was in complete linkage disequilibrium (LD) (D' = 1.0, r (2) = 1.0) with HLA-C rs10484554 C/T polymorphism. When the HLA-C rs10484554 CC homozygote genotype was used as the reference group, the TT/CT genotypes were associated with a significantly decreased risk for RA (adjusted OR = 0.72, 95% CI = 0.52-0.99, p = 0.044). We found that the HLA-C rs12191877 C/T polymorphism was also associated with a decreased risk of RA. HLA-C rs12212594 T/C, JAM2 rs2829866 A/T and REL rs702873 G/A polymorphisms were not associated with the risk of RA. These results provide evidence that HLA-C polymorphisms are associated with a decreased risk of RA.

Polymorphisms of VEGF, TGFβ1, TGFβR2 and conotruncal heart defects in a Chinese population

Genetic variants may determine susceptibility of congenital heart disease (CHD). To evaluate the impact of transforming growth factor-β1 (TGFβ1), TGFβ receptor II (TGFβR2) and vascular endothelial growth factor (VEGF) polymorphisms on conotruncal heart defects susceptibility, we genotyped six functional polymorphisms TGFβ1 rs1800469 C>T, TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T in a hospital based case-control study of 244 conotruncal heart defects cases and 136 non-CHD controls in a Chinese population. Logistic regression analyses revealed that if the TGFβ1 rs1800469 CC homozygote genotype was used as the reference group, subjects carrying the CT variant heterozygote had a significant 0.48-fold decreased risk of conotruncal heart defects [odds ratio (OR) = 0.52; 95% confidence interval (CI) = 0.30-0.88], subjects carrying the TT variant homozygote had a significant 0.47-fold decreased risk of conotruncal heart defects (OR 0.53; 95% CI 0.28-1.00). In stratification analyses, the TGFβ1 rs1800469 C>T genotype was associated with a decreased risk for tetralogy of fallot in homozygote comparisons (OR 0.47; 95% CI 0.22-0.99), a decreased risk for transposition of great artery in the dominant genetic model (OR 0.49; 95 % CI 0.28-0.87) and heterozygote comparisons (OR 0.45; 95% CI 0.24-0.83). Our findings suggest that TGFβ1 rs1800469 C>T polymorphism was significantly associated with decreased risk of conotruncal heart defects. TGFβR2 rs3087465 G>A, VEGF -2578C>A, -1498T>C, -634G>C and +936C>T polymorphisms may not play a role in the susceptibility of conotruncal heart defects.