AC Genotype Research Articles

Genetic Polymorphisms in miR-137 and Its Target Genes, TCF4 and CACNA1C, Contribute to the Risk of Bipolar Disorder: A Preliminary Case-Control Study and Bioinformatics Analysis.

Accumulating evidence has suggested that miR-137 and its target genes, CACNA1C, and TCF4, are amongst the most robustly implicated genes in psychiatric disorders. This preliminary study is aimed at investigating the effects of genetic variations in miR-137 (rs1625579A/C), TCF4 (rs1261084C/T), and CACNA1C (rs10774053A/G and rs10466907G/T) on BD susceptibility. We recruited 252 BD patients and 213 healthy subjects as the control group. Genotyping was performed using PCR-RFLP and ARMS-PCR methods. Enhanced risk of BD was found under the codominant homozygous, dominant, and allelic models of TCF4 rs1261084C/T, codominant homozygous and allelic models of CACNA1C rs10466907G/T polymorphisms, as well as codominant homozygous, dominant, recessive, and allelic models of the CACNA1C rs10774053A/G. Moreover, both TT/AG/GT/AA and TT/GG/GT/AC genotype combinations strongly increased the risk of BD in the participants. The bioinformatics analyses revealed that rs1261084C/T and rs10466907G/T created and disrupted binding sites of some miRNAs in the 3′-untranslated region of TCF4 and CACNA1C genes. In contrast, the rs10774053A/G created a new binding site for a major splicing factor and might have an effective role in the function of the CACNA1C protein. We have found that all the studied SNPs are positively associated with BD susceptibility. Replicated studies on different ethnicities are required to confirm these findings.

Association analysis and expression level of ACE polymorphisms with egg-laying trait in Taihang chicken

The number of egg-laying is an important indicator of reproduction performance in poultry breeding. To investigate the relationship between the function of Angiotensin-converting enzyme (ACE) and egg-laying performance of Taihang chicken, the mRNA and protein expression and single nucleotide polymorphism (SNP) of ACE were detected. Analysis of ACE bioinformatics and association analysis of polymorphisms were then performed. The polymorphisms analysis of ACE showed that three SNP loci (g.5066812A>C, g.5080076G>A, and g.5072728A>G) were detected in 800 Taihang chickens with egg-laying records. Association analysis of egg-laying found that ACE g.5066812A>C mutation was significantly associated with the egg-laying performance of Taihang chickens (P < 0.05), and the individuals with the g.5066812A>C mutation showed significantly increasing egg-laying. The mRNA expression was significantly higher in individuals with the AA genotype mutation than those with the AC and CC genotypes (P < 0.01), and the expression of ACE protein levels was consistent with the mRNA expression. Bioinformatics analysis indicated that these mutations affected the secondary and tertiary structure of ACE. This study provides new insights into ACE affecting chicken egg production and some basis for improving the egg production rate of Taihang chickens.

Fyn and Lyn gene polymorphisms impact the risk of thyroid cancer.

Thyroid cancer is the most common malignancy of the endocrine glands, and during last couple of decades, its incidence has risen alarmingly, across the globe. Etiology of thyroid cancer is still debatable. There are a few worth mentioning risk factors which contribute to initiation of abnormalities in thyroid gland leading to cancer. Genetic instability is major risk factors in thyroid carcinogenesis. Among the genetic factors, the Src family of genes (Src, Yes1, Fyn and Lyn) have been implicated in many cancers but there is little data regarding the association of these (Src, Yes1, Fyn and Lyn) genes with thyroid carcinogenesis. Fyn and Lyn genes of Src family found engaged in proliferation, migration, invasion, angiogenesis, and metastasis in different cancers. This study was planned to examine the effect of Fyn and Lyn SNPs on thyroid cancer risk in Pakistani population in 500 patients and 500 controls. Three polymorphisms of Fyn gene (rs6916861, rs2182644 and rs12910) and three polymorphisms of Lyn gene (rs2668011, rs45587541 and rs45489500) were analyzed using Tetra-primer ARMS-PCR followed by DNA sequencing. SNP rs6916861 of Fyn gene mutant genotype (CC) showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs2182644 of Fyn gene, mutant genotype (AA) indicated statistically significant 17-fold increased risk of thyroid cancer (P < 0.0001). Statistically significant threefold increased risk of thyroid cancer was observed in genotype AC (P < 0.0001) of Fyn gene polymorphism rs12910. In SNP rs2668011 of Lyn gene, TT genotype showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs45587541 of Lyn gene, GA genotypes showed statistically significant 11-fold increased risk in thyroid cancer (P < 0.0001). Haplotype analysis revealed that AAATAG*, AGACAG*, AGCCAA*, AGCCAG*, CAATAG*, CGCCAG* and CGCCGA* haplotypes of Fyn and Lyn polymorphisms are associated with increased thyroid cancer risk. These results showed that genotypes and allele distribution of Fyn and Lyn are significantly linked with increased thyroid cancer risk and could be genetic adjuster for said disease.

Interaction of fluoride exposure and CREB1 gene polymorphisms on thyroid function in school-age children

To evaluate the effects of CREB1 gene polymorphisms and long-term exposure to fluoride on thyroid function of children. A total of 424 children (including 226 boys and 198 girls) aged 7-12 years old were enrolled in Kaifeng, China by cross-sectional study in 2017. The concentrations of urinary fluoride (UF) and creatinine (UCr) were measured using fluoride ion-selective electrode assay and creatinine assay kit (picric acid method), respectively. The concentration of UCr-adjusted UF (CUF) was calculated. Children were divided into high fluoride exposure group (HFG, CUF >1.41mg/L) and low fluoride exposure group (LFG, CUF ≤1.41mg/L) according to the median concentration of CUF (1.41mg/L). The serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyronine (TT4) levels were detected by the radiation immunoassay. The B-mode ultrasound was performed to test the thyroid volume (Tvol). Genotyping of CREB1 gene was conducted by a custom-by-design 48-plex SNPscan™ Kit. Associations between CUF concentration, CREB1 single nucleotide polymorphisms (SNPs) and thyroid function were assessed by multiple linear regression models. Negative and positive associations between serum TT4 level (β=-0.721, 95%CI: -1.209, -0.234) and Tvol (β=0.031, 95%CI: 0.011, 0.050) and CUF concentration were observed respectively. Children carrying CREB1 rs11904814 TG and rs2254137 AC genotypes had lower TT3 levels (P<0.05). Children in HFG carrying rs11904814 TT, rs2253206 GG genotypes and rs6740584 C allele easily manifested lower serum TT4 levels (P<0.05). Moreover, interactions between excessive fluoride exposure and CREB1 SNPs on Tvol were observed, and the interaction among different loci of CREB1 gene could modify serum TT3 level (P<0.05, respectively). Fluoride could alter children's serum TT4 levels and Tvol. Interactions between fluoride exposure and CREB1 polymorphisms may modify thyroid volume of children.

Investigating whether microsatellites could influence the relative expression level of TLR4 gene in bursa of Rhode Island Red chicken

TLR4 gene, vitally linked to resistance to infection with Salmonella enteric serovar Typhimurium in chickens, was chosen as a candidate gene for this investigation to assess the probable impact of microsatellite genotypes on relative expression of TLR4 gene. Our study documented variable expression level of TLR4 gene in tissue bursa of RIR chicken encoded with different microsatellite genotypes. The DD and CC genotypes of MCW0330 microsatellite demonstrated numerically higher mRNA expression than its AA, AC and BD genotypes. Therefore, The MCW0330 genotyping may predict TLR4 gene expression if confirmed by a thorough investigation taking a large number of samples and then would play an important role in host-pathogen genetics with respect to Salmonellosis in poultry.

NLRP3 rs1539019 is significantly associated with chronic obstructive pulmonary disease in a Chinese Han population: a case-control study.

COPD is a complex respiratory disease characterized by chronic airway inflammation and the airflow limitations are not fully reversible due to the combination of genetic and environmental factors. Genetic factors such as polymorphisms, may affect the susceptibility of COPD. In the present study, we examined the association between the polymorphisms of three genes and COPD risk in a Chinese Han population. A total of 375 COPD patients and 284 control subjects were recruited from November 2018 to June 2021. Data on demographic basic information, smoking status, history of coal dust exposure, and peripheral blood were collected from subjects of two groups. Three polymorphisms (NLRP3 rs1539019, LAMB1 rs4320486, IL-6 rs1800796) were analyzed. Logistic analysis was used to evaluate the genetic contribution of selected SNPs to COPD susceptibility. The AC genotype of NLRP3 rs1539019 significantly decreased COPD risk compared with CC genotype (adjusted OR = 0.508, 95% CI 0.336-0.767). In the stratification analyses, the AC genotype significantly decreased the risk of COPD in subjects aged 60 and over (p=0.005; adjusted OR = 0.553; 95% CI 0.366-0.835) with current smoking status (p=0.002; adjusted OR = 0.419; 95% CI 0.240-0.732) when compared with AA+CC genotype. Moreover, a significantly decreased risk for GOLD III COPD was found in genotype AC of NLRP3 rs1539019 (p=0.006; adjusted OR = 0.502; 95% CI 0.306-0.822). Our present study revealed that the genotype AC of NLRP3 rs1539019 is related to a decreased risk of COPD in a Chinese Han population, a large-sample, multi-center, multi-ethnic study is needed to further confirm our study.

Vitamin D Receptor Genetic Polymorphisms Associate With a Decreased Susceptibility to Extremity Osteomyelitis Partly by Inhibiting Macrophage Apoptosis Through Inhibition of Excessive ROS Production via VDR-Bmi1 Signaling.

Background: Previous studies had reported that vitamin D receptor (VDR) gene polymorphisms were related to the development of several inflammatory disorders. However, potential links between such variations and the risk of developing a bone infection and underlying mechanisms remain unclear. This study aimed to analyze potential associations between VDR genetic variations and susceptibility to extremity osteomyelitis (OM) in a Chinese Han population and investigate potential mechanisms. Methods: Between January 2016 and August 2020, altogether 398 OM patients and 368 healthy controls were genotyped for six VDR gene polymorphisms, including ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), TaqI (rs731236), GATA (rs4516035), and Cdx-2 (rs11568820) by the SNaPshot genotyping method. Then, male C57BL/6 mice were randomly divided into vitamin D–standard, –excess, –deficient, and –rescued groups. One week after making the model surgery, OM occurrence and severity were assessed using the bacterial count and histopathological staining. In vitro, phagocytosis, apoptosis, and bactericidal ability of macrophages were evaluated by overexpression or knockdown of VDR protein. Results: Significant associations were found among rs7975232, rs1544410, and OM development by the recessive model (AA vs. AC + CC, p = 0.037, OR = 0.594), homozygous model (AA vs. CC, p = 0.033, OR = 0.575), and heterozygous model (CT vs. CC, p = 0.049, OR = 0.610), respectively. Patients with the AA genotype of rs7975232 had a relatively higher mean level of vitamin D than those with AC and CC genotypes (22.5 vs. 20.7 vs. 19.0 ng/ml). Similarly, patients with CT genotype of rs1544410 had a relatively higher mean vitamin D level than those with CC genotype (20.94 vs. 19.89 ng/ml). Outcomes of in vivo experiments showed that the femoral bacterial load of vitamin D–deficient mice was highest among different vitamin D dose groups, with the most severe histopathological features of infection, and vitamin D supplementation partly reversed the changes. While in vitro experiment results revealed that active vitamin D promoted phagocytosis and sterilization of macrophages and inhibited apoptosis during infection. Reactive oxygen species (ROS) inhibitor inhibited apoptosis of macrophages induced by bacterial infection. Active vitamin D inhibited excessive ROS production in macrophages via the VDR-Bmi1 signaling pathway. Conclusion: In this Chinese cohort, ApaI and BsmI are associated with a decreased risk of OM development by influencing serological vitamin D level, the latter of which reduced macrophage apoptosis with inhibition of excessive ROS production via the VDR-Bmi1 signaling pathway.

The Genetic Variants in the Renin-Angiotensin System and the Risk of Heart Failure in Polish Patients.

(1) Background: Heart failure (HF) is a complex disease and one of the major causes of morbidity and mortality in the world. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF. (2) Aim: To investigate the association of RAS key genetic variants, rs5051 (A-6G) in the gene encoding angiotensinogen (AGT), rs4646994 (I/D) in the gene for angiotensin I converting enzyme (ACE), and rs5186 (A1166C) in the gene encoding type 1 receptor for angiotensin II (AGTR1), with the HF risk in the cohort of Polish patients. (3) Methods: The study group consisted of 415 patients that were diagnosed with HF, while the control group comprised of 152 healthy individuals. Genomic DNA were extracted from blood and genotyping was carried out using either PCR or PCR-RFLP for ACE or AGT and AGTR1 variants, respectively. (4) Results: No association has been found between the I/D ACE and heart failure. The HF risk was significantly higher for AG AGT heterozygotes (overdominance: AG versus AA + GG) and for carriers of the G AGT allele in codominant and dominant modes of inheritance. However, the risk of HF was significantly lower in the carriers of at least one C AGTR1 allele (AC or CC genotypes) or in AC AGTR1 heterozygotes (overdominant mode). There was a significant relationship for AGT and HF patients in NYHA Class I-II for whom the risk was higher for the carriers of the G allele, and for the AG heterozygotes. There was also a significant interaction between heterozygote advantage of AGT and BMI increasing the risk for HF. (5) Conclusion: Our results suggest that the A(-6)G AGT polymorphism may be associated with HF in the Polish population and the HF risk seems to be modulated by the A1166C AGTR1 polymorphism.

Effect of TNF-α gene polymorphism on fertility insufficiency in Holstein cows

The current study was conducted in private station located in the middle of Iraq by using 100 blood samples from 100 Holstein cows to isolate DNA and determine the genotypes of TNF-α gene in tow regions on reproductive performance. Results showed two alleles with co-dominance and three genotypes was detected in 1st position (4th exon), the allele frequency was 0.695 and 0.305 for A and C allele respectively. The allele frequency in 2nd region (Flank region) was 0.64 and 0.36 for A and G allele respectively. Results showed a significant effect of gene polymorphism in 4th exon on retained placenta rate which differed significantly (P≤0.01) among cow groups, the highest rate was recorded in cows with cows with AC genotype about 0.24. A significant effect of gene polymorphism in 4th exon on ovulation weakness rate, the highest rate was recorded in cows with cows with CC genotype about 0.12. Parturition difficulties rate differed significantly (P≤0.01) , the highest rate was recorded in cows with mutant genotype namely,0.18. Results showed a significant effect of gene polymorphism in flank region, retained placenta rate was differed significantly (P≤0.01) among cow groups, the highest rate was recorded in cows with GC genotype about 0.20.

Genetic Variant of Vascular Endothelial Growth Factor (VEGF)-A rs699947 is Associated with Preeclampsia

Background: Preeclampsia remains as the leading cause of maternal-neonatal mortality and morbidity worldwide. Vascular endothelial growth factor A (VEGF-A) is a proangiogenic factor related to endothelial dysfunction and plays an important role in the preeclampsia pathophysiology. Genetic variants of VEGF-A are associated with VEGF-A expression and preeclampsia risk, however there are still inconsistent results between different populations. The aim of this study was to determine the association of this genetic variant as preeclampsia risk factor.Materials and methods: A cross-sectional study was performed with 76 pregnant women (29 preeclampsia and 47 normotensive) Jambi-Malay ethnic subjects. Sample DNA was extracted from subject’s blood. To determine the genotype, one-step tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) method for VEGF-A rs699947 C/A was used.Results: We found that pregnant woman with AC genotype (p-value=0.045; OR=2.76 ; 95% CI=1.01-7.58) and AA genotype (p-value=0.026; OR=12.44; 95% CI=1.23-126.18) had higher risk of preeclampsia than the CC genotype.Conclusion: Genetic variant VEGF-A rs699947 C/A is associated with preeclampsia. The AC and AA genotype is the risk genotype for preeclampsia in Jambi-Malay ethnics.Keywords: preeclampsia, VEGF-A, genetic variant, Jambi-Malay, Indonesia

Correlation Analysis of Cytochrome P450 SNPs in Hepatitis B-Caused Cirrhosis Patients

Aim. The aim of the present research was to find the correlation of single nucleotide polymorphisms (SNPs) of cytochrome P450 (CYP450) and hepatitis B-caused cirrhosis. Methods. Collection of specimens was done from 297 volunteers with confirmed hepatitis B-caused cirrhosis as well as 120 healthy volunteers in China. Individuals were categorized into three classes, i.e., A, B, and C, on the basis of the Child-Pugh-Turcotte (CPT) value of diseased people, while the Child-Pugh-Turcotte score was determined by rating the below mentioned 5 parameters, i.e., serum volume of bilirubin as well as albumin, prothrombin time, ascites, and encephalopathy. Twenty-four SNPs in the CYP450 superfamily including CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CY3A4 were detected using the SNaPshot assay. Results. CYP1A2-G2964A, CYP1A2-C733A, and CYP1A2-T5347C in all 24 SNP loci attained significance. AA genotype at CYP1A2-G2964A (P=0.048) and CC genotype at CYP1A2-T5347C (P=0.049) were significantly correlated with hepatitis B-caused cirrhosis. Moreover, an allele at CYP1A2-G2964A (P=0.032) and C allele at CYP1A2-T5347C (P=0.016) were associated with hepatitis B-caused cirrhosis. Furthermore, AC plus AA genotype at CYP1A2-C733A correlated with a TCM syndrome, “damp abundance due to spleen asthenia syndrome” (P=0.039) in individuals suffering from hepatitis B-resulted cirrhosis. Conclusion. The findings of the current study suggested that AA genotype at CYP1A2-G2964A and CC genotype at CYP1A2-T5347C may be higher risk in the occurrence of hepatitis B-caused cirrhosis. Moreover, patients with AC plus AA genotype at CYP1A2-C733A may be susceptible to appear having “damp abundance due to spleen asthenia syndrome.”

Significant Contribution of Interleukin-18 Genotypes to Lung Cancer Risk in Taiwanese.

The elevated expression of interleukin-18 (IL-18) among lung cancer patients raised our curiosity to examine the role of IL-18 genotypes in lung cancer. IL-18 -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 358 lung cancer cases and 716 controls were determined via the PCR-RFLP methodology. The distributions of genotypic and allelic frequencies of IL-18 -607, but not those of -656 or -137, were differentially distributed between cases and controls. IL-18 -607 AC and CC genotypes were both lower (45.8% and 16.2%) in lung cancer patients compared to controls (51.4% and 24.7%). In addition, IL-18 -607 AC and CC genotypes were of significantly lower percentages both among non-smokers and smokers. Otherwise, no differential distribution was found regarding IL-18 -656 or -137. IL-18 -607 C allele can serve as a protective predictor for lung cancer risk in Taiwanese.

Study of XPD Gene Polymorphism in HCV Positive HCC Egyptian Patients

Background: Hepatocellular carcinoma (HCC) is one of the most frequently occurring tumorous cells globally, but its pathogenesis is unknown. Xeroderma pigmentosum gene D (XPD) is a critical Repair of DNA gene that has been implicated in protein mutation. Aim: The objectives of this research were to assess the relationship between the XPD gene polymorphism (rs13181) (codon 751, Lys to Gln) and susceptibility to hepatocellular neoplasms, as well as to investigate the relationship between HCV and XPD polymorphisms. Methods: Seventy-nine HCC patients and 63 patients with active HCV infection, and 52 healthy controls were involved. Real-time PCR carried out for genotyping of XPD Lys751Gln (rs 13181). Results: Patients with XPD Lys751Gln AC genotype have a great risk of HCC development (p = 0.01, OR =1.505). Conclusion: Our finding was that XPD Lys751Gln (A/C) polymorphism exhibit a major function in HCC early detection susceptibility in Egyptian patients. It has the potential to be a valuable noninvasive molecular indicator for evaluating the HCC threat. Keywords: HCC; RT-PCR; XPD gene polymorphism

Hepcidin (rs10421768), Transferrin (rs3811647, rs1049296) and Transferrin Receptor 2 (rs7385804) Gene Polymorphism Might Be Associated with the Origin of Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which there is a multifocal damage to the nerve tissue. Additionally, the literature emphasizes the excessive accumulation of iron in the central nervous system of patients, which is negatively correlated with their psychophysical fitness. Iron metabolism genes polymorphisms may modulate iron deposition in the body and thus affect the clinical course of MS. We aimed to assess the frequency of HAMP, TFR2, and TF polymorphisms in MS patients and their impact on the clinical course of the disease. The studied polymorphisms were identified by the Real-Time PCR using TaqMan technology. Neurological assessment by means of EDSS scale was conducted. This cross-sectional study included 176 patients, with the mean age of onset of symptoms at 30.6 years. The frequency of alleles of the studied polymorphisms was as follows: (a) HAMP rs10421768: A 75.9% (n = 267), G 24.1% (n = 65), (b) TF rs1049296: C 89.2% (n = 314), T 10.8% (n = 38), (c) TF rs3811647: A 39.8% (n = 140), G 60.2% (n = 212), (d) TFR2 rs7385804: A 59.1% (n = 59.1%), C 40.9% (n = 144). In the codominant inheritance model of TF rs1049269, it was shown that people with the CT genotype scored statistically significantly lower points in the EDSS scale at the time of diagnosis than those with the CC genotype (CC Me = 1.5, CT Me = 1.0 p = 0.0236). In the recessive model of TF inheritance rs3811647, it was noticed that the primary relapses were significantly more frequent in patients with at least one G allele compared with those with the AA genotype (AG + GG = 81.2%, AA = 18.8%, p = 0.0354). In the overdominant model rs7385804 TFR2, it was shown that among patients with the AA genotype, multiple sclerosis occurs significantly more often in relatives in a straight line compared with people with the AC and CC genotypes (AA = 100.0%, AC + CC = 0.0%, p = 0.0437). We concluded that the studied polymorphisms might affect the clinical course of MS.

FOXP3 Gene Variants in Patients with Systemic Lupus Erythematosus: Association with Disease Susceptibility in Men and Relationship with Abortion in Women.

FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases. To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients' characteristics. Genotyping was performed on 265 patients with SLE and 404 healthy controls using PCR-RFLP. Patients' demographic, laboratory, and clinical information were all documented. The relationship between the SNPs and patients' characteristics was statistically analyzed. The frequency of C/- genotype in male patients was significantly higher than in the healthy male controls, whereas the frequency of A/- genotype was lower (OR=0.53; 95% CI=0.28-1.00, p=.05). Analysis of the correlation between these SNPs and the patients' characteristics showed a longer disease duration in the rs3761548 C/- carriers and a correlation with arthralgia in both SNPs. In the females, there was a significant association between CC haplotype and disease susceptibility (OR=0.6, CI=0.38-0.94, p=.027). A significant association of both SNPs with the history of abortion was also detected. The frequencies of the rs3761548 AA (p=.006) and the rs2294021 CC genotypes (p=.038) and AC/AC combination (p=.033) were higher in women who had an abortion. We found a correlation between the rs3761548 AC genotype and the decreased C4 level and cardiovascular involvement, and the rs2294021 CC genotype with ESR, neurological involvement, and photosensitivity. FOXP3 rs3761548 C/- genotype association with disease susceptibility in male patients, an association of both SNPs with the abortion risk in female patients, and the correlation between these SNPs and several clinical features of the patients suggest their association with the disease development and pathology.

P2X7 1513A/C loss-of-function polymorphism and active tuberculosis disease in a cohort of Egyptian population: a pilot study

BackgroundTuberculosis (TB) is a multifactorial disease, and increasing evidence shows that genetic variants in regulating genes of immune response confer susceptibility to active TB at the individual level. We aimed to identify the contribution of P2X7 receptor 1513A/C genetic polymorphisms to different clinical forms of active tuberculosis in a cohort of Egyptian population.MethodsA case–control study that enrolled 25 newly diagnosed pulmonary TB (PTB) patients by positive sputum for AFB or positive culture, 25 extrapulmonary TB (EPTB) diagnosed by pathological/bacteriological/immunological studies and 25 healthy controls. A blood sample was taken before starting of therapy for P2X7 1513A/C polymorphism genotyping using PCR-restriction fragment length polymorphism.ResultsFifty-two percent of the participants were in the third decade with equal gender distribution. P2X7 receptor 1513AA (homozygote wild), AC (heterozygote) and CC (homozygote mutant) genotypes were identified. AC and CC genotypes distribution were significantly more frequent in the active TB cases (either PTB or EPTB) rather than controls (p < 0.05). Further, P2X7 1513A/C genotypes’ distribution did not associate with old TB or gender (p > 0.05), but significantly associated with history of smoking (x2 trend analysis p = 0.036).ConclusionsThere is positive association between P2X7 receptor 1513A/C polymorphism and active tuberculosis in the Egyptians.

Polymorphisms of an oncogenic gene, mesothelin, predict the risk and prognosis of gastric cancer in a Chinese Han population.

Mesothelin (MSLN) is a cell surface protein associated with tumor invasion and metastasis. This study aims to explore the biological function of MSLN in gastric cancer and to evaluate the association of MSLN polymorphism (rs3764247, rs3764246, rs12597489, rs1057147, rs3765319) with the risk and prognosis of gastric cancer. Small interfering RNA (siRNA) transfection and MSLN overexpression were performed in human gastric cancer cell lines, respectively. The proliferation of tumor cells was evaluated by Cell counting kit 8(CCK-8) and colony formation assay. Wound healing assay and transwell assay were used to elucidate gastric cancer cell migration and invasion rates. We conducted a case-control study involving 860 patients with gastric cancer and 870 controls. All mutation sites were genotyped by PCR-LDR sequencing. First, our study revealed the cancer-promoting role of MSLN in gastric cancer. Second, we also demonstrated that rs3764247 and rs3764246 were associated with a reduced risk of gastric cancer (OR = 0.83, p = 0.010; OR = 0.84, p = 0.011; respectively). The clinicopathological analysis further showed that rs3764247 was closely related to T stage, vascular infiltration, and HER2 expression. In addition, in the survival analysis of 392 patients with gastric cancer, patients with rs3764247 CC genotype had poorer survival than patients with AA + AC genotype after adjusting for age, sex, TNM stage, and Lauren classification (HR = 2.07, p = 0.029). Our findings indicated that MSLN could be an oncogene whose polymorphisms were closely related to the risk and prognosis of gastric cancer.

Single Nucleotide Polymorphism in the 3' Untranslated Region of PRKAA2 on Cardiometabolic Parameters in Type 2 Diabetes Mellitus Patients Who Received Metformin.

PurposeThis study aimed to explore the association of rs857148 A>C as 3ʹUTR variants with blood pressure, HbA1c profile, and lipid profiles as cardiometabolic parameters among patients with T2DM receiving metformin.Patients and MethodsThis cross-sectional analytic research was conducted with 114 consecutively selected patients with T2DM. Polymerase chain reaction-restriction fragment length polymorphism was conducted to determine rs857148. A total of 108 patients fulfilled inclusion and exclusion criteria.ResultsGenotype distribution agreed with the Hardy Weinberg Equation for Equilibrium (p>0.05) but wildtype allele was found as the minor allele. Subjects with CC genotype and C allele had enhanced HbA1c levels (OR=7.12; 95% CI=1.05–48.26; p=0.04; OR=1.66; 95% CI=1.06–2.60; p=0.03, respectively). It was confirmed by dominant model whereas subjects with AA tended to have reduced HbA1c compared to AC+CC genotype (OR=0.15; 95% CI=0.02–0.97; p=0.047). AC genotype had significant correlation to total cholesterol (OR=1.05; 95% CI=1.01–1.10; p=0.03) compared to AA genotype.ConclusionWe conclude that polymorphism of rs87148, specifically CC genotype and C allele, has a significant association with HbA1c and total cholesterol after considering oral hypoglycemia agent dose, age, gender, and combination therapy, compared to AA genotype. Future studies that involve a larger sample population and more rigorous selection criteria are required.

Association of AGTR1 A1166C and CYP2C9∗3 Gene Polymorphisms with the Antihypertensive Effect of Valsartan.

Background The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor (AGTR1) gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 (CYP2C9) gene polymorphism (CYP2C9∗3). Methods 281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the AGTR1 and CYP2C9 gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group (n = 144, SBP/DBP <140/90 mmHg) and poorly controlled group (n = 137, SBP/DBP ≥140/90 mmHg). Results Older age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of AGTR1 A1166C were detected in the well-controlled than the poorly controlled patients (P = 0.005 and P = 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of AGTR1 A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199–6.705, P = 0.018). No significant difference was observed in the allele or genotype distribution of CYP2C9∗3 polymorphism between well-controlled and poorly controlled patients. Conclusions The current data suggested that the AGTR1 A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.

A Proposed TUSC7/miR-211/Nurr1 ceRNET Might Potentially be Disturbed by a cer-SNP rs2615499 in Breast Cancer

Evidence and in silico analyses showed that TUSC7, miR-211, and Nurr1 may be involved in BC pathogenesis by ceRNET signaling axis. This study aimed to investigate the potential role of TUSC7/miR-211/Nurr1 ceRNET and rs2615499 variant as a novel cer-SNP in BC subjects. The expression assays were conducted by qPCR on tumor tissues (n = 50), tumor-adjacent normal tissues (TANTs) (n = 50), and clinically healthy control tissues (n = 50). The expression of TUSC7 and Nurr1 significantly decreased, but the level of miR-211 significantly increased in tumor tissues compared to TANTs and healthy normal tissues. Altered expression of TUSC7 and miR-211 was associated with poor prognosis of patients. The Nurr1 exhibited a double-edged sword-like activity in BC. In addition, TUSC7, Nurr1, and miR-211 expressions were significantly related to a novel BC-associated rs2615499 (A > C) located in the miR-211 binding site on Nurr1 3'-UTR. In the second part of the study, a case-control study was performed on BC patients (n = 100) and matched healthy controls (n = 100). The genomic DNA was isolated and genotyping was performed using Tetra-Primer ARMS PCR. The CC and AC genotypes were associated with higher expression levels of Nurr1 and worse outcomes of the disease. Our findings revealed that TUSC7 functions as a tumor suppressor in BC potentially via miR-211/Nurr1, which might be disturbed by the cer-SNP rs2615499. However, functional studies are needed to validate these results.