Association of APC and MUTYH Mutations with Colorectal Cancer

PurposeColorectal cancer (CRC) is one of the most fatal cancers in the world. Determining if the risk of polymorphism alleles for CRC could contribute to clinical situations suggestive of an increased genetic risk for CRC is of significant importance. The aim of this study was to evaluate the association of genetic polymorphisms in two genes, APC and MUTYH, with CRC susceptibility in Iranian society. MethodsIn this experimental study, DNA was extracted from 200 blood samples (100 control and 100 patients with CRC). After identifying point mutations in APC and MUTYH genes and designing primers, they were examined by Tetra-arms PCR technique. Chi-square test was used to calculate and analyze the statistical and frequency of SNP in patients and control groups. ResultsSNPs: rs121913333, rs77542170, rs1801166 and rs869312753 showed significant association with CRC. rs121913333 on 5q22 appeared to have the highest degree of correlation with CRC (P=0.0001). ConclusionOur findings indicate that APC and MUTYH mutations are related to the incidence of colorectal cancer. Not only mutant but also heterozygous genotype has a significant role in CRC development.

A Family Screening of CD19 Gene Mutation by Restriction Fragment Length Polymorphism

Background: CD19 molecule found on B lymphocyte surface forms CD19 complex together with CD21, CD81, CD225 in mature B cells and regulates B lymphocyte activation with antigen stimulation. Mutation(s) in the gene encoding the CD19 molecule affect CD19 protein expression and primary immunodeficiency (PID) occurs. Some genetic method, especially sanger and next generation sequencing and flow cytometric methods are widely used in the diagnosis of PID. The RFLP method, which is faster and cheaper than other mutation detection methods, is rarely used in the diagnosis of PID. The study aimed to genetically identify CD19 deficiency, which is a PID, using the RFLP method. Methods: The study was performed at Necmettin Erbakan University, Meram Medicine Faculty Hospital, Pediatric Allergy and Immunology clinic. A total of 8 patients and two healthy controls could be included in the study. A total of 8 patients and two healthy controls were included in the study, and the relevant region genotypes in the CD19 gene were determined by performing RCR-RFLP analysis. Results: CD19 deficiency was first described by us. The index case, newborn baby and mother were also included in the study. It was determined that the index case (P6) was homozygous mutant, the newborn baby (P7) and mother (P8) had heterozygous genotype. Based on this situation, one child (P1) was found to be homozygous mutant, mother (P2), father (P3) and other children (P4 and P5) had heterozygous genotype in the family, which was determined to be related to the first case. Conclusion: Rapid genetic diagnosis in patients suspected of having a known case of PID insufficiency as a result of clinical and laboratory findings carries a vital risk in terms of treatment options to be offered to patients. Although PCR-RFLP, which is a cheap, safe and fast method, is used to detect known mutations, the use of PID is rare. In our study, it has been shown that it is a method that can be used in the diagnosis of PID by determining genotypes using PCR-RFLP, and especially in terms of rapid genetic testing of family screenings.

Genetic polymorphisms in the mEH gene in relation to tobacco smoking: role in lung cancer susceptibility and survival in north Indian patients with lung cancer undergoing platinum-based chemotherapy

Aim: Epoxide hydrolase is involved in oxidative defenses and is responsible for the activation of carcinogens. The relationship between EPHX1 polymorphisms (Tyr113His and His139Arg) and overall survival (OS) and lung cancer (LC) risk was investigated. Methods: The study comprised 550 cases and 550 controls. Genotyping and statistical analysis were applied. Results: The variant genotypes of EPHX1 polymorphisms exhibited no association with LC risk. The Tyr113His polymorphism exhibited twofold increased odds of lymph node invasion (p = 0.04). The Tyr/His genotype is a risk factor for smokers. Subjects carrying the combined genotype for His139Arg showed better median survival time (MST) and the heterozygous genotype revealed better MST in the case of small-cell lung cancer (SCLC; 11.30 vs 6.73 months; log-rank test: p = 0.02). The heterozygous genotype (His139Arg) had longer MST in patients receiving cisplatin/carboplatin and irinotecan (11.30 vs 7.23; log-rank test: p = 0.007) Conclusion: The Tyr113His polymorphism is associated with LC risk in smokers and is a potential prognostic factor for OS in patients with SCLC after irinotecan.

Two Novel Disease-Causing Variants in the PDE6C Gene Underlying Achromatopsia

We report the clinical phenotype and genetic findings of two variants in PDE6C underlying achromatopsia (ACHM). Four patients with the variant c.1670G&#x3e;A in exon 13 of the PDE6C gene were identified. Additionally, one had compound heterozygous genotype, with two variants in the <i>PDE6C</i> gene, a variant of c.2192G&#x3e;A in exon 18 and c.1670G&#x3e;A in exon 13. All patients presented the symptomatic triad of decreased visual acuity, severe photophobia, and colour vision disturbances. SD-OCT showed an absence of the ellipsoid zone, creating an optically empty cavity at the fovea in three patients. The patient with the compound heterozygous genotype presented a more severe subfoveal outer retina atrophy. ERG recordings showed extinguished responses under photopic and 30-Hz flicker stimulation, with a normal rod response. We identified two new variants in the <i>PDE6C</i> gene that leads to ACHM.

Association of Single Nucleotide Polymorphism LEP-R c.668A>G (p.Gln223Arg, rs1137101) of leptin receptor gene with endometrial cancer

Background The aim of this study was to analyze the frequencies of genotypes and alleles of Single Nucleotide Polymorphism (SNP) LEP-R c.668A>G (p.Gln223Arg, rs1137101) of leptin receptor gene and to assess the influence this DNA marker has on endometrial cancer (EC) with respect to total body fat content. Methods The study comprised 120 patients treated for endometrial cancer and 90 controls treated for uterine fibroids. In total, 210 patients were included in this research. DNA was isolated from archival post-operative specimens. Polymerase Chain Reaction – Restriction Fragment Length Polymorphism was employed to analyze the SNP. Results In this paper we have demonstrated that heterozygous genotype AG of SNP LEP-R c.668A>G (p.Gln223Arg, rs1137101) is statistically less frequent in women with endometrial cancer (EC) than in controls: 33 versus 57%, respectively. Similarly, this heterozygous genotype is statistically significantly less frequent in obese (BMI > 30) women with EC than in lean controls (BMI < 25): 30 versus 63%, respectively. Conclusions AG polymorphic variant of SNP LEP-R c.668A>G (p.Gln223Arg, rs1137101) in LEP-R may be considered a protective factor in the development of endometrial cancer.

Appropriate growth models to describe early growth of Kejobong goat based on Growth Hormone (GH) gene sequence analysis

The objectives of this study were to reveal appropriate growth models describing early growth of Kejobong goat based on Growth Hormone (GH) gene sequence analysis. A total of 35 DNA samples and 1.960 records of quantitative traits of Kejobong goat were collected. The exon 3 of GH gene was amplified and was sequenced to determine the SNP. Body weight and body measurements of the goats were taken at 0-14 weeks of age. Four non-linear growth models were applied for analysis of growth to compare growth performance of different genotypes by Non-Linear Mixed Model. A non-synonymous mutation (g1170AG) genotyped into GG, AG and AA was significantly associated with growth traits. Animals with heterozygous genotype AG showed higher growth traits than animals with homozygous genotype AA. Nonetheless, animals with homozygous genotype GG had the same growth traits with those animals with heterozygous genotype AG and homozygous genotype AA. The most fitted model for describing body weight was Von Bertalanffy model, while for describing wither height and hip height was Brody model. SNP at exon 3 of the GH gene can be used as genetic marker for improvement of growth traits of Kejobong goats.

Gene Polymorphisms of the Renin-Angiotensin-Aldosterone System as Risk Factors for the Development of In-Stent Restenosis in Patients with Stable Coronary Artery Disease

This study investigated the renin-angiotensin-aldosterone system (RAAS) gene polymorphisms as possible genetic risk factors for the restenosis development in patients with drug-eluting stents. 113 participants had coronary artery disease and underwent stenting. The control group consisted of 62 individuals with intact coronary arteries. Patients were divided into two groups: with in-stent restenosis (ISR) and without it. The patients with ISR were classified into subgroups by the terms of the restenosis development and age. Real-time PCR and Restriction Fragment Length Polymorphism-PCR were used to genotype the study participants for RAAS gene polymorphisms. We found that the development of restenosis is generally associated with the minor A allele for renin (REN) rs2368564 and the major TT genotype for angiotensinogen (AGT) rs699. The heterozygous genotype for AGT rs4762 acts as a protective marker. A minor A allele for angiotensin II type 2 receptor (AGTR2) rs1403543 is associated with a risk of restenosis in people under 65 years old. Among patients with the early ISR, heterozygotes for angiotensin II type 1 receptor (AGTR1) rs5186 are more frequent, as well as A allele carriers for AGTR2 rs1403543. A minor homozygous genotype for REN rs41317140 and heterozygous genotype for aldosterone synthase (CYP11B2) rs1799998 are predisposed to the late restenosis. Thus, to choose the effective treatment tactics for patients with coronary artery disease, it is necessary to genotype patients for the RAAS polymorphisms, which, along with age and clinical characteristics, will allow a comprehensive assessment of the risk of the restenosis development after stenting.

POLYMORPHISM OF BETA-CASEIN GENE IN THE KHOLMOGOR CATTLE BREED

Исследован полиморфизм гена β-казеина (CSN2) у холмогорской породы крупного рогатого скота (169 коров, 101 бык) из хозяйств Архангельской области и Республики Коми. Анализ ДНК проводили методом ПЦР с искусственно созданным сайтом рестрикции (ACRS). В стадах холмогорского скота Республики Коми частота аллеля А2 варьировала от 0,412 до 0,599, в целом преобладал аллель А2 гена β-казеина с частотой 0,557. Половина животных (49%) имела гетерозиготный генотип, 20% — обладали гомозиготным генотипом А1А1 и 31% — являлись гомозиготными по аллелю А2 β-казеина. В стадах холмогорского скота Архангельской области частота аллеля А2 была в целом ниже, чем в Республике Коми (0,466). Чаще встречался аллель А1 β-казеина (0,534). Большинство особей (45%) имели гетерозиготный генотип, 31% животных имели гомозиготный генотип А1А1 и 24% — А2А2. Показатель частоты встречаемости аллеля А2 в различных стадах Архангельской области отличался высокой степенью вариабельности от 0,238 до 0,692. Анализ полученных данных свидетельствует о том, что частота встречаемости аллелей и генотипов β-казеина в значительной степени зависит от особенностей ведения селекционно-племенной работы в хозяйстве. The polymorphism of the beta-casein (CSN2) gene was studied in the Kholmogor breed of cattle (169 cows, 101 bulls) from the farms of the Arkhangelsk region and the Komi Republic. DNA analysis was performed by PCR with an artificially created restriction site (ACRS). In the herds of Kholmogor cattle of the Komi Republic, the frequency of the A2 allele varied from 0.412 to 0.599, in general, the A2 allele of the β-casein gene prevailed with a frequency of 0.557. Half of the animals (49%) had a heterozygous genotype, 20% had a homozygous A1A1 genotype, and 31% were homozygous for the A2 β-casein allele. In the herds of Kholmogor cattle of the Arkhangelsk region, the frequency of the A2 allele was generally lower than in the Komi Republic (0.466). The A1 allele of β-casein was more common (0.534). The majority of individuals (45%) had a heterozygous genotype, 31% of animals had a homozygous genotype A1A1 and 24% — A2A2. The frequency of occurrence of the A2 allele in various herds of the Arkhangelsk region was characterized by a high degree of variability from 0.238 to 0.692. The analysis of the obtained data shows that the frequency of occurrence of alleles and genotypes of β-casein largely depends on the peculiarities of conducting breeding work on the farm.

Association of Interleukin-18 genotypes (-607 C>A ) and (-137 G>C) with the hepatitis B virus disease progression to hepatocellular carcinoma

Chronic infection with HBV has been reported to be associated with the development of HCC. The inflammation mounted by cytokine mediated immune system plays an important role in the pathogenesis of HBV associated HCC. IL-18 is a pro-inflammatory cytokine whose role in the development of HBV associated chronic to malignant disease state has not been much studied. The present study was conceived to determine the role of genetic polymorphisms in IL-18, serum levels of IL-18 and expression level of its signal transducers in the HBV disease progression. A total of 403 subjects were enrolled for this study including 102 healthy subjects and 301 patients with HBV infection in different diseased categories. Polymorphism was determined using PCR-RFLP. Genotypic distributions between the groups were compared using odd’s ratio and 95% CI were calculated to express the relative risk. Circulating IL-18 levels were determined by ELISA. Expression level of pSTAT1 and pNFƙB were determined by western blotting. In case of IL-18(-607C > A), the heterozygous genotype (CA) was found to be a protective factor while in case of IL-18(-137G > C) the heterozygous genotype (GC) acted as a risk factor for disease progression from HBV to HCC. Moreover, serum IL-18 levels were significantly increased during HBV disease progression to HCC as compared to controls. Also the levels of activated signal transducers (pSTAT1 and pNF-κB) of IL-18 in stimulated PBMCs were significantly increased during HBV to HCC disease progression. These findings suggest that IL-18 has the potential to act as a biomarker of HBV related disease progression to HCC.

Features of genetic manifestations in patients with abdominal obesity during atrial fibrillation in combination with arterial hypertension

Aim. To study the significance of the rs1378942 polymorphisms of the CSK gene and rs2200733 (chromosome 4q25) in the progression of AF in men with AH and AO. Materials and methods. In an observational cohort study, 116 men aged 4565 years were followed. Of these, 57 patients with AF, AH and AO and a control group including 59 patients with AF, AH and without AO. Testing of polymorphism rs1378942 of the CSK gene and rs2200733 of chromosome 4q25 using polymerase chain reaction with restriction fragment length polymorphism. All statistical calculations were performed using the Rstudio program (version 0.99.879 20092016 RStudio, Inc., USA). Results. The average age of all studied patients was 53.37.1 years. When dividing patients with AF and AH into groups based on the presence/absence of AO, it turned out that in the subgroups of carriers of different genotypes of the rs1378942 polymorphism of the CSK gene there are significant differences in BMI: in the group with BMI, there is an increase in the indicator in the series of CC, AC, AA genotypes. The highest BMI value in carriers of the CC genotype (p0.03) was in the group with AO. In the subgroups of carriers of different rs2200733 genotypes of chromosome 4q25, CC has the highest BMI (p0.05). It was proved that in the group with AO, the progression of AF occurred 2.57 times more often than in the group without AO (p0.003). Conclusion. In men with AF and AH, single nucleotide polymorphisms rs1378942 of the CSK gene and rs2200733 of chromosome 4q25 are associated with BMI. The heterozygous genotype AC rs1378942 in the CSK gene is significantly more common in patients, regardless of the presence of AO. In the group with AO, the progression of AF occurred 2.57 times more often than in the group without AO.