CG Genotype Research Articles

Influence of growth hormone gene polymorphism on the productive qualities and the level of toxic elements in the hair of Kalmyk breed calves

The studies were performed on a model of calves of the Kalmyk breed (n = 100) from birth to 14 months of age. The effect of growth hormone polymorphism (rs135322669) on productive qualities, body parameters, and toxic load level is estimated. Blood samples were taken to detect gene polymorphism. DNA samples were isolated from whole blood using a DNA-Extran-1 reagent kit. Primers were developed based on published bGH sequences (Gen Bank Accession NOS. M57764) using Primer3 software. Real-time PCR was performed on an ANK-32 programmable amplifier. The frequency of occurrence of polymorphism in the calves was revealed: 62 % with the CC genotype, 26 % with CG and 12 % with GG. The study of the growth rate of the studied animals from birth to 14 months of age was carried out on the basis of individual monthly weighing. The development was studied on the basis of taking measurements: height at the withers, height at the sacrum, width of the chest, depth of the chest, length of the body, width at the sacrum at 14 months of age. The superiority of calves with CC genotype in live weight starting from 6 months of age over peers with genotypes CG and GG was established. At the age of 6 months it was 5.0–7.0 %, and at 14 months of age 5.0–9.0 %. Calves with the GG genotype were inferior to peers with the CC genotype in height at the withers by 2.3 %, by 2.0 % in the sacrum, by 4.7 % in the chest width, by 5.3 % in the width at the sacrum, by 3.1 % in the chest depth and were inferior to the calves with genotype CG by the width of the chest by 2.3 %. The determination of toxic elements: Al, Cd, Pb, Sn, Hg, Sr, was carried out by atomic emission and mass spectrometry (AES-ICP and MS-ICP). Calves with the SS genotype accumulated less toxic substances in the hair from the withers, so their ∑tox was 52.4-63.1 % lower as compared to their peers with the CG and GG genotypes. This is also confirmed by the correlation analysis, which revealed a reliable relationship between gene polymorphism and ∑tox in wool at the level of r = 0.92.

Association between SNP rs527616 in lncRNA AQP4-AS1 and susceptibility to breast cancer in a southern Brazilian population.

Breast cancer (BC) is the leading cause of death by this disease in women worldwide. Among the factors involved in tumorigenesis, long non-coding RNAs (lncRNAs) and their differential expression have been associated. Differences in gene expression may be triggered by variations in DNA sequence, including single nucleotide polymorphisms (SNPs). In the present study, we analyzed the rs527616 (C>G), located in the lncRNA AQP4-AS1, using PCR-SSP in 306 BC patients and 312 controls, from a Brazilian population. In the BC group, the frequency found for CG heterozygotes was above the expected and the overdominant model is the best one to explain our results (OR: 1.70, IC 95%: 1.23-2.34, P<0.001). Furthermore, the SNP were associated with age at BC diagnosis and the risk genotype more frequent in the older age group. According to TCGA data, AQP4-AS1 is down-regulated in BC tissue, and the overexpression is associated with better prognoses, including Luminal A, HER2-, stage 1 of disease and smaller tumor. In conclusion, the CG genotype is associated with increased susceptibility in the southern Brazilian population. This SNP is mapped in the lncRNA AQP4-AS1, showing differential expression in BC samples. Based on these results, we emphasize the potential of the role of AQP4-AS1 in cancer.

Associations of IL-1β and IL-6 gene polymorphisms with Parkinson's disease.

The aim of this study was to explore the associations of interleukin-1β (IL-1β) and IL-6 gene polymorphisms with the pathogenesis of Parkinson's disease. A total of 200 patients with Parkinson's disease in our hospital were collected as the disease group. Meanwhile, 200 healthy subjects were taken as the control group. Peripheral blood samples were drawn from all research subjects. The polymorphic regions of IL-1β and IL-6 were amplified via polymerase chain reaction (PCR). Moreover, the polymorphisms were detected and analyzed, followed by further analysis based on the changes in gene expressions and Hoehn-Yahr grade of patients. The allele distributions at IL-1β rs571556428 (p=0.015) and IL-6 rs543214973 (p=0.012) were statistically different between control group and disease group. In disease group, the G allele frequency at IL-1β rs571556428 and T allele frequency at IL-6 rs543214973 were significantly higher (p<0.05). Genotype distributions at IL-1β rs572292175 (p=0.017) and rs571556428 (p=0.000), and IL-6 rs543214973 (p=0.002) in disease group were also different from those in control group. In addition, the frequencies of CT genotype at IL-1β rs572292175, AA genotype at IL-1β rs571556428 and AA genotype at IL-6 rs543214973 in disease group were significantly lower (p<0.05). After modeling and analysis, it was found that the distribution of recessive model at IL-1β rs571556428 (p=0.012) and IL-6 rs543214973 (p=0.014) in disease group exhibited significant differences from those in control group. The frequencies of TA haplotype at IL-1β rs572292175 and rs571556428 (p=0.038) and GA haplotype at IL-6 rs1474348 and rs543214973 (p=0.047) in disease group were lower than those in control group (p<0.05). The polymorphisms at IL-1β rs571556428 and IL-6 rs1474348 were significantly associated with gene expression (p<0.05). Moreover, the expressions of IL-1β and IL-6 rose significantly in patients with GG genotype at rs571556428 and CG genotype at rs1474348, respectively (p<0.05). Furthermore, the polymorphism at IL-1β rs571556428 was significantly correlated with the grade of Parkinson's disease (p=0.000). Parkinson's disease was in a higher grade (grade 4-5) in patients with AA genotype, whereas in a lower grade (grade 1-2) in patients with GG and AG genotypes. IL-1β and IL-6 gene polymorphisms are significantly associated with the pathogenesis of Parkinson's disease.

ASSOCIATION ANALYSIS OF PIOGLITAZONE EFFECTIVENESS IN TREATMENT OF NAFLD PATIENTS WITH OBESITY AND PPARG RS1801282 (PRO12ALA) GENOTYPE

The aim: To study the association between the effectiveness of treatment with pioglitazone non-alcoholic fatty liver disease (NAFLD) in patients with obesity and PPARG rs1801282 (Pro12Ala)-polymorphism in Ukrainians. Materials and methods: 123 patients with NAFLD in combination with obesity 1, 2, 3 classes were included in comprehensive weight loss program (5 visits, 12-weeks). The case group was treated with pioglitazone 15 mg / day, while the control group received only program. Ultrasound (US) steatometry and genetic testing rs1801282 polymorphism in PPARG gene were performed. Results: Pioglitazone, PPARG rs1801282 genotype, CAP before treatment, previous weight loss attempts, and duration of obesity were associated with the change in controlled attenuation parameter (CAP) during treatment. There was a significant association between the target CAP reduction achievement and pioglitazone treatment (adjusted odds ratio 0.23, 95% CI 0.07–0.73; p = 0.01) with the CC genotype of PPARG gene (adjusted odds ratio 92.9, 95% CI 7.4–1159; p &lt; 0.001) compared to patients with the CG genotype. Conclusions: Pioglitazone and PPARG rs1801282 polymorphism could influence on dynamics of CAP reduction during treatment.

DDAH2 (-449 G/C) G allele is positively associated with leukoaraiosis in northeastern China: a double-blind, intergroup comparison, case-control study.

Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase (DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this double-blind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, SmaI restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2 (-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models (GG and CG), while 89.13% of healthy control subjects had dominant genetic models (CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls (P = 0.0002). The frequency of G alleles in the leukoaraiosis patients (71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower (χ2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes (Kruskal-Wallis H = 24.5955, P < 0.0001). In addition, the GG genotype of DDAH2 (-449 G/C) was more common in patients with leukoaraiosis. These findings suggest that the G allele of DDAH2 (-449 G/C) is a risk factor for leukoaraiosis morbidity and is correlated with high levels of asymmetric dimethylarginine. This study was approved by the Institutional Ethics Committee of The 2nd Affiliated Hospital of Harbin Medical University of China (approval No. KY2016-177) on July 28, 2016.

Genetic Variations in Cytochrome P450 1A1 and 1B1 Genes in a Cohort of Patients from Iraq Diagnosed with Breast Cancer.

Breast cancer is the most prevalent malignant neoplasm in females. Genetic variations in the xenobiotic metabolising cytochrome enzymes; Family 1 Subfamily A Member 1 (CYP1A1) and Family 1 Subfamily B Member 1 (CYP1B1) might play a role in the individual susceptibility to breast cancer and its prognosis. The goal of this study is to estimate the incidence of single nucleotide polymorphisms (SNPs) in CYP1A1 (rs1048943, Ile462VaI, and rs4646903/MSP1) and in CYP1B1 (rs1056836, Leu432Val) genes in patients with breast cancer. This case-control study included 180 female patients with breast cancer and 180 healthy control subjects from Kirkuk/Iraq. Genomic DNA was extracted from venous blood samples and tested for SNPs by the direct DNA sequencing technique. A statistical analysis was done to identify if there is any association between SNPs and the increasing odd of breast cancer and its stage, grade and molecular subtype at diagnosis. The common (reference) genotype of CYP1A1 gene rs1048943 is AA. The AG and GG variant genotypes were significantly more common in the breast cancer patients and conferred an increased odd of breast cancer and its later stages (stages III and IV) and poor differentiation (P < .01) but not with the molecular subtypes. The common genotype of CYP1A1 rs4646903 is TT. The variant genotypes TC and CC are not associated either with increased risk of breast cancer (P > .05) or with its stage, grade or molecular subtypes (P > .05). The GG genotype of CYP1B1 rs1056836 was the common genotype. The CG and CC variant genotypes were not associated with the increased risks of breast cancer (P > .05) or its stage, grade or molecular subtypes (P > .05). In conclusion, variants genotypes of CYP1A1 rs1048943 might play a role in breast cancer pathogenesis and prognosis and can have a place in cancer screening and tailored medicine in the future in the Iraqi population. Future larger scale studies including other genes might help to better understand the role of the SNP in breast risk and its prognosis.

Technology for detecting highly productive animals based on elemental status assessment

The studies were conducted on bull-calves of the Kalmyk breed (n = 100), age 12 months, live weight 326.4 ± 6.4 kg. In the course of the research, we performed a sampling of animal biosubstrates. The article studies a single nucleotide polymorphism of the growth hormone gene (rs135322669). The elemental composition of biosubstrates was determined by 25 indicators, by atomic emission and mass spectrometry (AES-ICP and MS-ICP). It was found that the frequency of occurrence of CC alleles in the sample was 62.0 %, CG – 26.0 and GG – 12.0 %, χ2Эмп=39.924,2 test – 5.99. Evaluation of the elemental status of calf bull revealed significant differences depending on the polymorphism in the bovine growth hormone gene. In bulls with the CC genotype, the exchange pool Ca, K, Na, Co, Cr, Cu, J, Se, B, Si, Li, V was significantly higher compared to the CG genotype; and Ca, K, Na, J, Se, B, Li in comparison with the GG genotype. CC genotypes to GG were characterized by the accumulation of toxic elements: Al, Pb, Hg, Cd. Consequently, under the same ecological conditions of breeding in calf bull with the CC genotype, the detoxification mechanisms are higher, which is reflected in the reduced concentration of toxic elements in the wool. A technology for identifying highly productive animals is proposed based on the selection of bulls by the level of toxic elements in wool, calculated on the basis of the sum of moles: Al, Cd, Hg, Pb, Sn, Sr at 8 months of age, which allows increasing productivity by 9.4-15.6%. It was concluded that there is a need to continue the research with the obligatory safety assessment of the toxic elements of the resulting meat products.

Association of -634 C/G Polymorphism at Vascular Endothelial Growth Factor Gene with Risk Retinopathy of Prematurity

Background: Retinopathy of prematurity (ROP) is a major cause of blindness in newborn infants worldwide. It is well known that neovascularization of the retina is prominent in the proliferative stages of ROP. It is suggested that vascular endothelial growth factor (VEGF) may play a role in the development of ROP. The aim of this study was to evaluate the association of the VEGF -634C/G polymorphism at VEGF with risk of ROP. Methods: In the study 54 neonates diagnosed with ROP and 55 healthy neonates served as controls. The VEGF -634 C/G polymorphism was genotyped by restriction fragment length polymorphism (PCR-RFLP) technique. Results: The CC, CG, and GG genotypes of VEGF -634C/G polymorphism were found in 33.3%, 38.9%, and 27.8% of neonates with ROP, respectively. In controls, CC, CG, and GG genotypes were seen in 43.6%, 45.4%, and 10.9%, respectively. Frequency of mutant allele (C) was 52.8% in neonates with ROP and 66.4% in healthy neonates. There was a significant difference in the distribution of VEGF -634C/G polymorphisms between cases and controls. Moreover, there was a significant association between VEGF -634C/G polymorphisms and ROP risk (OR = 3.141, 95% CI 1.115-8.851, P = 0.030). Conclusion: This study results revealed that VEGF -634C/G polymorphism might serve as a risk factor for development of ROP. Thus, clinicians should be aware of the ROP risk in infant with the VEGF -634C/G polymorphism and ROP risk in infants. However, large sample size and well-designed studies are necessary to validate our findings.

Association of Adiponectin−11377 C/G (rs266729) Gene Polymorphism with Nonalcoholic Fatty Liver Disease and Metabolic Features in Egyptian Women

The present cross-sectional study included 150 unrelated non-alcoholic fatty liver disease (NAFLD) patients and 150 healthy subjects. ADIPOQ (-11377C / G) variant was genotyped with polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) method for both patients and controls. Anthropometric and biochemistry parameters were measured. The Homeostasis Model Insulin Resistance Assessment (HOMA-IR) was used to assess the insulin resistance. The rs266729 polymorphism was associated with NAFLD with significant increase in CG genotype compared to those with the wild genotype CC (OR = 9.24, 95% CI = 4.96 - 17.21, p<0.001) in co dominant tested inheritance model as well in dominant tested inheritance model with CG/GG genotype (OR = 9.58, 95% CI = 5.32 – 17.28, p< 0.001). The G allele increased the risk of NAFLD (OR = 6.06, 95% CI = 3.65 - 10.05, p< 0.001) in comparison with C allele. Subgroup comparison in NAFLD revealed significant higher levels of waist circumference (WHR), HOMA-IR, systolic blood pressure (SBP), fasting glucose and LDL-C in GG and GC carriers compared to CC genotype and significant lower levels of serum adiponectin. Conclusions: The study suggests that ADIPOQ gene polymorphism can be used as a helpful biomarker for NAFLD and abnormal metabolic parameters. Our study sheds light on its role that might be played in the pathogenesis of NAFLD. Proper evaluation of NAFLD is likely to improve therapy effectiveness and safety management.

Genetic Association of Interleukin-6 Polymorphism (rs1800796) with Chronic Hepatitis B Virus Infection in Chinese Han Population.

Hepatitis B virus (HBV) infection is a global health care burden that can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. We conducted this study to identify the association between interleukin-6 (IL-6) gene rs1800796 (-572G/C) polymorphism and the risk of chronic HBV infection in adults. A total of 1,048 participants including 518 cases and 530 controls were recruited for this study. The Mass Array time-of-flight mass spectrometer was applied for single-nucleotide polymorphism rs1800796 genotyping. There was a significant correlation between genotype CG in rs1800796 and chronic HBV infection in the Chinese Han population (odds ratio [OR] = 0.759, 95% confidence interval [CI]: 0.586-0.983, p = 0.04), which was also observed at allele G (OR = 0.800, 95% CI: 0.657-0.975, p = 0.02). Furthermore, significant differences in the ≤45 years old group (CC vs. CG+GG, OR = 0.616, 95% CI: 0.413-0.918, p = 0.02) and in the male group (CC vs. CG+GG, OR = 0.666, 95% CI: 0.483-0.920, p = 0.01) were found in the subgroups analysis. Our data revealed a significant association of IL-6 rs1800796 with the risk of chronic HBV infection in the Chinese Han population; meanwhile, age and gender are two coordinative risk factors, which provides new clues for the study of susceptibility of chronic HBV infection in adults.

Association between Allelic Variations of -174G/C Polymorphism of Interleukin-6 Gene and Chronic Kidney Disease-Mineral and Bone Disorder in Iraqi Patients

This study designed to examine association between-174G/C polymorphism of interleukin-6 gene and phosphate, calcium, vitamin D3, and parathyroid hormone levels in Iraqi patient with chronic kidney disease on maintenance hemodialysis. Seventy chronic renal failure patients (patients group) and 20 healthy subjects (control group) were genotyped for interleukin-6 polymorphism and genotyping was performed by conventional polymerase chain reaction-restriction fragment length polymorphism. No significant differences in phosphate levels were observed in patients and control with different interleukin-6 genotypes. Control had non-significant differences in calcium levels, while patients with GG and CG genotypes displayed significant elevation with time. Conversely, control and patients with GG and CC genotypes had significant elevation in vitamin D3 levels with time. Regarding parathyroid hormone, control had non-significant differences, while patients with GG and CC genotypes displayed significant elevation with time.&#x0D; Patients with GG genotype displayed significant changes in calcium, vitamin D3 and parathyroid hormone levels with time.

THE RS1801282 PPARG POLYMORPHISM DEPENDENT METABOLIC EFFECTS OF PIOGLITAZONE IN PATIENTS WITH OBESITY AND CONCOMITANT NAFLD

The aim: to investigate the metabolic effects of different treatment options in patients with obesity and concomitant non-alcoholic fatty liver disease (NAFLD) based on the presence of CG and GG genotypes PPARG rs1801282 (Pro12Ala) polymorphism in Ukrainians. Materials and methods: 123 patients with NAFLD in combination with obesity 1, 2, 3 classes were included in the motivational weight loss program (5 visits, 3 months). The case group was treated with pioglitazone 15 mg / day, while the control group received only a program. Ultrasound steatometry, anthropometric and laboratory tests before and after treatment, genetic testing rs1801282 polymorphism in PPARG gene were performed. Results: the carriers of CG and GG genotypes PPARG rs1801282 polymorphism had less high stimulated insulin levels compared with groups of different genotypes (p&lt;0.001). It was found pioglitazone effectiveness with significant difference in dynamics of CAP reduction (p&lt;0.001) regardless of polymorphism. Dynamics of BMI decrease was the lowest in control group CC carries – –2.81 (–3.23; –2.39) kg (p&lt;0.001) compared among other groups. Subjects from pioglitazone group with rs1801282 polymorphism carrying of CG and GG genotypes had significant differences in dynamics of fasting С-peptide decrease, serum uric acid reduction – –1.31 (–1.50; –1.13) µg/L and -165.3 (–182.80; –147.80) µmol/L (p&lt;0.001) respectively compared among other groups. Conclusions: Better reduction of metabolic parameters during pioglitazone treatment of patients with obesity and concomitant NAFLD appears to be associated with carrying of CG and GG genotypes PPARG rs1801282 polymorphism.

The prognostic factors for effectiveness of the treatment of non-alcoholic fatty liver disease against the obesity background

Objective — to investigate the role of pioglitazone, PPARg Pro12Ala (rs1801282) polymorphism, primary results of steatometry and obesity anamnestic data in the effectiveness of treatment non‑alcoholic fatty liver disease (NAFLD) co‑occurring with obesity.Materials and methods. The study involved 123 patients with obesity of 1 ‑3 degree and NAFLD. The patients were randomized into two groups (and 4 groups for multiple‑pairwise comparison based on variant of PPARg gene), comparable in age and sex. The patients of the case group adhered to the basic recommendations for losing weight and received treatment with pioglitazone 15 mg/ day, patients of the comparison group receive non‑drug treatment only. All patients underwent a molecular genetic study of detecting PPARg Pro12Ala (rs1801282) polymorphism, as well as anthropometric measurements, laboratory and instrumental examinations (including Ultrasound (US) steatometry) before and after 12 weeks of treatment. In addition, weight loss history and self‑report adherence with the help of questionnaires were conducted.Results. Metabolic syndrome was found in 80.5 % of obese and NAFLD patients, impaired fasting glycaemia — in 13.82 %. The dynamics of BMI reduction was significantly the lowest –2.81 (–3.23; –2.39) kg (p < 0.001) in the comparison group of patients carrying CC genotype PPARg rs1801282 polymorphism compared among other groups. There was a significant association between the target reduction of the controlled attenuation parameter (≥ 0.33 dB/ cm) and treatment with pioglitazone 15 mg/ day (aOR 0.23; 95 % CI 0.07 — 0.73; p = 0.01) and the carries of CC genotype PPARg rs1801282 polymorphism (aOR 92.9 95 % CI 7.4 — 1159; p < 0.001) compared with the carries of CG genotype. We also identified significant associations with primary results of steatometry (0.1 dB/ cm) (aOR 0.49; 95 % CI 0.34 — 0.70; p < 0.001), duration of obesity (5 years) (aOR 2.19; 95 % CI 1.25 — 3.84; p = 0.006) and number of previous weight loss attempts (for 2) (aOR 2.51; 95 % CI 1.76 — 3.58; p = 0.002).Conclusions. The results demonstrated that the following factors have an important prognostic value for the effectiveness of NAFLD treatment against the obesity background: pioglitazone in treatment scheme, especially in patients with CG genotype PPARg rs1801282 polymorphism, higher steatosis level, shorter duration of obesity and less number of previous weight loss attempts.

Functional correlations between CXCL10/IP10 gene polymorphisms and risk of Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis syndrome with unknown pathogen. The immune system has been suggested to involve in the pathogenesis in KD. IP10 is a chemoattractant for initiating T-cell activation. The aim of this study was to investigate the association between genetic polymorphisms of IP10 and KD. A total of 354 KD patients and 1,709 control subjects (709 subjects in cohort 1 and 1,000 subjects in cohort 2) were enrolled in this study. Four tagging single nucleotide polymorphisms (rs3921, rs4256246, rs4508917, and rs4386624) were chosen for genotyping. Our results indicated thatCC genotype of rs3921 and GG genotype of rs4386624 had higher frequency in KD patients compared to control. In addition, higher plasma IP10 level wasobserved in CC genotype of rs3921 than CG genotype and GG genotype. C/G haplotype carriers of rs3921/rs4386624 had 5.48-fold risk for KD compared to G/C haplotype carriers. Two-locus analysis further showed the combinatorial effects of rs3921 and rs4386624 in KD susceptibility. This study indicated the close correlation between IP10 and the risk of Kawasaki disease.

Lack of association of HFE gene polymorphism with high body iron status in Pakistani patients with type 2 diabetes mellitus.

The Aim of this study was to investigate the relationship of 3 common polymorphisms in the HFE gene (C282Y, H63D and S65C) with high body iron status in a population of Pakistani subjects with type 2 diabetes mellitus (DM) and to explore if there is any novel mutation in HFE gene in a sample of Pakistani subjects with type 2 DM. In a case-control design, 200 healthy controls and 200 consecutive adult subjects with type 2 DM (both gender; age range of 30-70 years) were enrolled with informed consent. Their serum samples were analyzed for body iron status (ratio of concentration of soluble transferrin receptor to ferritin concentration). DNA from blood was screened for HFE gene polymorphisms via polymerase chain reaction, followed by restriction fragment length polymorphism or via Sanger sequencing to identify any novel mutation(s) in HFE gene. We found that there was lack of any association between HFE polymorphism and body iron status in Pakistani subjects with type 2 DM and healthy controls. H63D was the most common polymorphism found in this population. Single base substitution of G nucleotide instead of C at the codon position 187 in the HFE gene exon 2 was discovered in one subject with DM. There was also a lack of association between D allele (variant allele of H63D) and type 2 DM. A significant relationship was found between CG genotype and abnormal albuminuria in subjects with type 2 DM (p = 0.036). In conclusion, HFE gene polymorphism is not associated either with high body iron status or type 2 DM in a hospital based Pakistani population and variant allele of H63D polymorphism appears to be associated with diabetic nephropathy.

The association between SNPs and hepatitis B virus related acute-on-chronic liver failure.

This study intended to investigate the association between ten single nucleotide polymorphisms (rs1143623, rs12692386, rs1799983, rs2297518, rs2910164, rs3129859, rs4251961, rs4846085, rs641738, rs873457) with susceptibility and prognosis of hepatitis B related acute-on-chronic liver failure (HBV-ACLF). This is a hospital-based case-control study included 274 patients with HBV-ACLF and 534 patients with chronic hepatitis B. The patients who were successfully followed were divided into the survival group and the death group according to the clinical outcome during the hospitalization and 90days after discharge. The ten SNPs were genotyped in all subjects by using imLDR. Genotype, allele frequency, dominant model, recessive model and codominant model were constructed to investigate the association between single nucleotide polymorphisms with susceptibility and prognosis of HBV-ACLF. The genotype distribution of rs1143623 was statistically different between the two groups (P=0.04), but the allele frequency was not statistically significant (P=0.44). GC and GG+CG genotypes at rs1143623 reduced the risk of HBV-ACLF. There were only two GG and GT genotypes in rs1799983 in our study, and the genotype and allele frequency were statistically different between the death group and the survival group (P=0.027, P=0.023). Patients with T allele may reduce the risk of death in patients with HBV-ACLF. The genotype and allele frequency of rs2297518 showed no significant difference. In dominant models, patients with GA+AA genotypes at rs2297518 had a reduced risk of death.

The relationship analysis of microRNA-146a rs2910164 polymorphism with risk of colorectal cancer in province of South-Khorasan, Iran

IntroductionColorectal cancer (CRC) is a health obstacle and one of the most prevalent reasons of neoplasm-linked death among of the different nations. The researches have revealed that occurrence of this neoplasm is influenced by environmental and genetic risk factors. Recently, it is reported the association of rs291016 polymorphism in microRNA-146a (miR-146a) gene with risk of different neoplasms such as CRC. In existent study, we have investigated role of this polymorphism in CRC risk for the first time in the province of South Khorasan, east of Iran. Materials and methodIn this research, the 54 people with CRC and 116 healthy people are selected from this province. After collecting blood samples and extracting genomic DNAs, the genotyping is conducted by PCR-RFLP technique. Finally, the data is analyzed using the SPSS program (16 version). ResultsAfter the data analysis and computing of odds ratio (OR) and P-value, it is detected the statistically important connections in comparison between rs291016 GG genotype and CC genotype (OR = 1.594, 95% CI = 1.380–1.841, P < 0.001), GG genotype versus CC + CG genotypes (OR = 1.681, 95% CI = 1.447–1.954, P < 0.001), G-wild allele compared to C-mutant allele (OR = 1.296, 95% CI = 1.208–1.390, P < 0.001) among case and control groups. ConclusionThe miR-146a rs2910164 GG genotype and G allele can be suggested as risk factors for occurrence of CRC in the studied patients.

Correlations of endothelin-1 gene polymorphisms and hypertensive intracerebral hemorrhage.

The aim of this study was to investigate the correlations of endothelin-1 (ET-1) gene polymorphisms with the occurrence of hypertensive intracerebral hemorrhage (HICH). In this case-control study, 100 HICH patients and 100 controls with matched race, age and gender were enrolled as research subjects. Single nucleotide polymorphisms (rs1920453, rs1022436 and rs1035627) in the promoter region of ET-1 gene were typed via conformational difference gel electrophoresis. Whether the distribution frequency of ET-1 genotypes conformed to Hardy-Weinberg equilibrium was evaluated by chi-square test. The correlations of different gene polymorphisms and alleles in the promoter region of ET-1 gene with the occurrence of HICH were analyzed. Furthermore, the associations of rs1920453 polymorphism in the promoter region of ET-1 gene with neurological deficit scores and laboratory parameters of HICH patients were explored. It was found that ET-1 gene polymorphisms (rs1920453, rs1022436 and rs1035627) conformed to Hardy-Weinberg equilibrium (p>0.05). Gene-based association analysis indicated that only rs1920453 polymorphism and alleles were correlated with the occurrence of HICH (p<0.05). However, rs1022436 and rs1035627 polymorphisms and alleles had no association with HICH (p>0.05). Additionally, NIHSS score and high-density lipoprotein cholesterol level were prominently higher in HICH patients with CG and GG genotypes of ET-1 gene polymorphism rs1920453 than those in patients with CC genotype (p<0.05). Rs1920453 in the promoter region of ET-1 gene is correlated with the occurrence of HICH.

PNPLA3 and TM6SF2 polymorphisms in Brazilian patients with nonalcoholic fatty liver disease.

BACKGROUNDNonalcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide, with significant morbidity associated with nonalcoholic steatohepatitis (NASH). Genome-wide association studies demonstrated that the variants rs738409 C/G in the PNPLA3 and rs58542926 C/T in the TM6SF2 genes are determinants of inter-individual and ethnicity-related differences in hepatic fat content and NAFLD progression.AIMTo investigate PNPLA3 and TM6SF2 genotype frequency and their association with NAFLD development and progression in Brazilian patients.METHODSThis cross-sectional case-control study enrolled 285 individuals from the Gastroenterology and Hepatology clinics at a university hospital in Brazil. The case patients (n = 148) were confirmed to have NAFLD by the identification of hepatic steatosis on ultrasonography and exclusion of other causes of liver disease. According to the clinical protocol, patients underwent liver biopsy when at high risk for NASH and/or advanced fibrosis (n = 65). Steatohepatitis was confirmed in 54 patients. Individuals who did not have biopsy indication or NASH on histology were considered to have simple steatosis (n = 94). The control group (n = 137) was selected among patients that attended the Intestinal Disease clinic and was composed of subjects without abnormalities on abdominal ultrasonography and normal liver biochemical tests. All individuals underwent PNPLA3 and TM6SF2 genotype analysis. RESULTSPNPLA3 CC, CG and GG genotype frequencies were 37%, 44% and 19%, respectively, in NAFLD patients and were 58%, 31% and 10% in controls (P < 0.001). In a model adjusted for gender, age, body mass index and type 2 diabetes mellitus, the G allele increased the chance of NAFLD (OR = 1.69, 95%CI: 1.21-2.36, P = 0.002) and NASH (OR = 3.50, 95%CI: 1.84-6.64, P < 0.001). The chance of NASH was even higher with GG homozygosis (OR = 5.53, 95%CI: 2.04-14.92, P = 0.001). No association was found between G allele and the features of metabolic syndrome. In histological assessment, PNPLA3 genotype was not associated with steatosis grade, although GG homozygosis increased the chance of significant NASH activity (OR = 17.11, 95%CI: 1.87-156.25, P = 0.01) and fibrosis (OR = 7.42, 95%CI: 1.55-34.47, P = 0.01) in the same adjusted model. TM6SF2 CC, CT and TT genotype frequencies were 83%, 15% and 0.7%, respectively, in NAFLD patients and were 84%, 16% and 0.7% in controls (P = 0.78). The T allele presence was not associated with NAFLD or NASH, and was not associated with histological features.CONCLUSIONPNPLA3 may be involved in susceptibility and progression of NAFLD and NASH in the Brazilian population. More advanced histological liver disease was associated with the G allele. The TM6SF2 genetic variants were not associated with NAFLD susceptibility and progressive histological forms in the population studied, but further studies are required to confirm these findings.

Interleukin-6 (174G/C) Gene Polymorphism and Serum Levels of IL-6, their Association with Risk of Obesity in Iraqi Childhood Populations

Background: Childhood obesity is one of the most serious public health challenges of the 21st century.Aim: The present study was conducted to investigate the association of CD14 genotype and serum levels ofIL-6 with risk of ischemic stroke.Method : A total of 60 patients with obesity were included in the study who were admitted to hospital fromthe period between March to August 2020, and other groups consist of 60 apparently healthy individuals. Afive ml of blood samples were collected, 3 ml of each sample for polymerase chain reaction amplificationand detection of IL-6 technique. The remaining (2 ml) for IL-6 serum levels by ELISA assay procedure.Results: IL-6 (-174G/C) genotype was significantly associated with increased risk of obesity (P = 0.004).However, IL-6 serum levels were higher in subjects with GG genotype compared with those with CG or CCgenotype (P &lt; 0.001).Conclusion: A significant correlation between IL-6 genotype and IL-6 levels were higher level in subjectswith GG genotype compared with those with CG or CC genotype.