Genetic polymorphisms of interluekin-17A gene in Black-clothes Zhuang population in Guangxi

The aim of the present study was to investigate whether there was any relationship between some DNA N-methyltransferase 1 (DNMT1) polymorphisms and susceptibility to idiopathic sudden sensorineural hearing loss (ISSHL) in ISSHL patients. We investigated 90 patients diagnosed with ISSHL and a control group composed of 75 age- and gender-matched healthy individuals. DNA was extracted from the blood samples by phenol-chloroform method. Polymerase chain reaction and restriction fragment length polymorphism methods were used for the genotyping analysis of 4 regions of DNMT1. For rs2228612 single nucleotide polymorphism (SNP), the frequency of AA, AG, and GG genotypes were 81.4%, 9.3%, and 9.3% in controls and 82.2%, 16.7%, and 1.1% in patients, respectively. We observed a significant decrease in the frequency of GG genotype in patients with ISSHL when compared with controls (p=0.027). The frequency of GG, AG, and AA genotypes for rs2228611 SNP were 20.7%, 49.3%, and 20% in controls and 20%, 47.8%, and 32.2% in patients, respectively. There was a significantly increased frequency of the AA genotype of this SNP in the DNMT1 gene, and we found that individuals with the AA genotype had 2.47 times the risk for ISSHL development than individuals with the GG genotype (p=0.41). The GAA haplotype may constitute 2.66 times the risk for ISSHL disease (OR=2.66, 95% confidence interval: 0.28-25.03). This study's results showed that the AA genotype in rs2228611 polymorphism was a risk factor in ISSHL patients and the GG genotype could be a protective factor in rs2228612 polymorphism.

Kawasaki disease (KD) is the most common autoimmune vasculitis syndrome in children, which supposed be a complex polygenic disorder. Interleukin-17 (IL-17) is a member of the pro-inflammatory cytokine family, which has a strong pro-inflammatory effect and can participate in various acute and chronic inflammatory responses. This study aims to investigate the relationship between the single-nucleotide polymorphism (SNP) locus rs3819025 in the IL-17A gene and the susceptibility to KD. A total of 120 patients with KD who met the diagnostic criteria (the KD group) and 120 healthy children (the control group) were enrolled retrospectively in this study. Polymerase chain reaction (PCR) and DNA direct sequencing were used to detect the SNPs of children in the 2 groups. The frequencies of GG, GA, and AA genotypes of rs3819025 locus in the IL-17A gene in the KD group were 82.5%, 17.5%, and 0, respectively, and the frequencies of GG, GA, and AA genotypes in the control group were 72.5%, 22.5%, and 5.0%, respectively. There were significant differences in both genotype (χ2=7.524, P=0.023). The allele frequencies G and A of rs3819025 locus in the KD group were 91.25% and 8.75%, respectively, while those in the control group were 83.75% and 16.25%, respectively. There was significant difference between the 2 groups (χ2=6.171, P=0.013). The distribution frequencies of GG or GA genotype and G or A allele were 88.46% or 11.54% and 94.23% or 5.77% in the KD group with coronary artery lesion, respectively. The distribution frequencies of GG or GA genotype and G or A allele were 78.72% or 21.28% and 89.36% or 10.64% in the KD group without coronary artery lesion, respectively. There were no significant differences in genotype and allele frequencies of rs3819025 between the KD with coronary artery lesion group and the KD group without coronary artery lesion (both P>0.05). Besides, children with the allele A had a 2.023 times higher risk of KD than those without the allele A (χ2=6.171, P=0.013; OR=2.023, 95% CI 1.151 to 3.557). The locus rs3819025 in the IL-17A gene is associated with the pathogenesis of KD. The allele A of the locus rs3819025 in the IL-17A gene may be a risk factor for KD.

Objective To investigate the possible correlation between the monocyte chemoattractant protein-1 ( MCP-1 ) gene A-2518G single nucleotide polymorphism (SNPs) in the promoter region and acute coronary syndrome (ACS) in Chinese Han ethnic population of Sunan region,Methods This study was conducted with a case-control design in 484 ACS patients including 290 acute myocardial infarction (AMI)patients and 194 patients with unstable angina pectoris (UAP) and 346 control subjects ruled out coronary disease by coronary angiography (control group),including 166 patients with coronary atherosclerosis and 180 subjects without coronary stenosis.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for the detection of the A-2518G polymorphism in MCP-1 gene,and then thefrequency of genetype was statistically analyzed.Results There were AA,AG and GG genotypes of MCP-1 gene A-2518G polymorphism in the ACS group and control group.The two groups could be considered as a genetic equilibrium representative by Hardy-Weinberg equilibrium ( P ＞ 0.05 ).Compared with the control group,the frequencies of AA genotype ( 15.32％ vs.16.12％ ),AG genotype (53.47％ vs.51.86％ ),GG genotype (31.21％ vs.32.02％ ) and G allele genotype (57.95％ vs.57.95％ ) in ACS group were not significantly different ( P was 0.083,0.673,0.821 and 1.00,respectively).Multivariate logistic regression analysis indicated that there was no significant correlation between MCP-1 gene A-2518G polymorphism and ACS regardless of differences in gender,age,smoking,diabetes,TG and LDL-C ( P ＞0.05 ).There was no significant difference in gender and age of ACS onset between two groups ( P ＞ 0.05).There were no significant differences in the frequencies of AA,AG and GG genotypes and G allele genotype among AMI group,UAP group and normal coronary group ( P ＞ 0.05).Conclusions The data shows that MCP-1 gene A-2518G polymorphism is not associated with the risk of ACS in the Chinese Han ethnic population living in Sunan region. Key words: Monocyte chemoattractant protein-1; Single nucleotide polymorphism; Acute coronary syndrome

Objective To study the relationship between monoeyte chemoattractant protein 1 (MCP-1)-2518A/G polymorphism and lung cancer in Han nationality of North China. Methods One hun-dred and thirty-four unrelated consecutive patients with lung cancer(112 with NSCLC, 22 with SCLC)and 82 healthy individuals were studied. The polymorphisms of MCP-1-2518A/G were detected with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results The distribution of AA, AG and GG genotypes of MCP-1-2518 was significantly different in lung cancer patients compared with controls (X~2=8. 486,P=0. 014). There was a significant increase in the frequency of the AA genotype (OR=2. 645, X~2=6. 532, P=0.011) and a significant decrease in the frequency of the GG genotype (OR=0.519, X~2=4.929, P=0. 026)in the lung cancer patients, compared with controls. In the NSCLC patients the fre-quency of the AA genotype was higher than controls(OR=3. 138, X~2=8. 905, P=0.003) and the frequency of the GG genotype was lower than controls(OR=0. 516 ,X~2=4. 613, P=0. 032). The frequencies of AA, AG and GG genotypes in SCLC patients and controls had no difference. Conclusion This preliminary study showed that MCP-1-2518A/G polymorphism was associated with NSCLC but not SCLC. Key words: Lung cancer; MCP-1 gene; Gene polymorphism

The distribution of polymorphic variants of innate immunity genes TLR9 (+2848G>A) and DEFB1(-20G>A; -44C>G; -52G>A) was evaluated in long-living individuals. No significant differences were found in the distribution of genotypes and alleles of the TLR9 gene. The following features were revealed: increase in the frequency of AA and GG genotypes and decrease in the frequency of the AG genotype of the DEFB1(-20G>A) gene; increase in the frequency of the CC genotype and C allele and decrease in the frequency of CG and GG genotypes and G allele of the DEFB1(44C>G) gene; and increase in the frequency of AA and AG genotypes and A allele and decrease in the frequency of the GG genotypes and G allele of the DEFB1(-52G>A) gene. Genotypes and alleles of the DEFB1 gene found in long-living individuals can be considered as the factors that increase the probability of longevity and favorable course of age-related diseases.

Genetic polymorphisms of very important pharmacogenomic (VIP) variants are important for personalized medicine. However, these have not been extensively studied in the Tibetan population. In this study, 82 VIP variants were detected in the Tibetan and Han (HAN) populations from northwestern China. Subsequently, we compared the differences between the Tibetan population and ten populations, including the HAN, Japanese in Tokyo (JPT), Mexican ancestry in Los Angeles (MEX), Toscans in Italy (TSI), African ancestry in Southwest USA (ASW), Luhya in California Webuye, Kenya (LWK), Gujarati Indians in Houston, Texas (GIH), Maasai in Kinyawa, Kenya (MKK), Yoruba in Ibadan, Nigeria (YRI), and Utah residents with Northern and Western European ancestry from the CEPH collection (CEU). Using the χ(2) test, we identified differences in the frequency distribution of 4, 4, 7, 10, 11, 11, 13, 15, 19, and 20 loci in the Tibetan population, compared to the HAN, JPT, MEX, TSI, ASW, LWK, GIH, MKK, YRI, and CEU populations, respectively [P < 0.05/(82*10)]. rs2115819, rs9934438, and rs689466, located in the ALOX5 (arachidonate 5-lipoxygenase), VKORC1 (vitamin K epoxide reductase complex, subunit 1) and PTGS2 (prostaglandin-endoperoxide synthase 2) genes, respectively, in the Tibetan population were different from those in most of the populations. Our results complement the information provided by the database of pharmacogenomics on Tibetan people, and provide an avenue for personalized treatment in the Tibetan population.

Genetic polymorphisms of pharmacogenomic VIP variants in the Kyrgyz population from northwest China

Background: Interleukin 17 (IL17) is a pro-inflammatory cytokine with pivotal modulatory effects on antitumor immune responses and has been reported to play a particularly important role in the occurrence and development of bladder cancer. We aimed to investigate the possible influence of IL17 genetic variations on loci rs22775913 and rs763780 with genetic susceptibility to bladder cancer in southern Iran. Method: In this case-control study, we enrolled 180 patients with urothelial bladder cancer (mean age 64 years) and 180 age/gender matched healthy controls without any family history of cancer and autoimmune disorders. Genomic DNA was extracted from peripheral whole blood and genotyping was performed using PCR-RFLP method. Results: Genotype distributions in both the patients and controls were in agreement with Hardy-Weinberg equilibrium. The frequency of GG, GA, and AA genotypes for IL17A were 87 (48.3%), 72 (40%), and 21 (11.7%) among patients; and 92 (51.1%), 75 (41.6%), and 13 (7.3%) in the controls. The frequency of AA, AG, and GG genotypes for IL17F in both the patients/controls were 160 (88.9%)/ 158 (87.8%), 16 (8.9%)/ 21 (11.7%), and 4 (2.2%)/ 1 (0.5%), respectively. Statistical analysis revealed no significant differences between the two groups regarding the frequency of genotypes and alleles (P>0.05). Conclusion: Our data collectively suggested that genetic variations on loci rs22775913 and rs763780 of IL17 genes were not associated with bladder cancer susceptibility in the Iranian population. Our finding has to be confirmed in different ethnic groups.

BackgroundSeveral genetic variants in the ATP-binding cassette transporter A1 (ABCA1) gene have associated with modifications of serum high-density lipoprotein cholesterol (HDL-C) levels and the susceptibility for coronary heart disease, but the findings are still controversial in diverse racial/ethnic groups. Bai Ku Yao is an isolated subgroup of the Yao minority in southern China. The present study was undertaken to detect the possible association of V825I (rs2066715) polymorphism in the ABCA1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.MethodsA total of 677 subjects of Bai Ku Yao and 646 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Polymerase chain reaction and restriction fragment length polymorphism assay combined with gel electrophoresis were performed for the genotyping of V825I variant, and then confirmed by direct sequencing.ResultsThe levels of serum total cholesterol (TC), HDL-C, apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of G and A alleles was 57.4% and 42.6% in Bai Ku Yao, and 57.7% and 42.3% in Han (P > 0.05); respectively. The frequency of GG, GA and AA genotypes was 33.7%, 47.4% and 18.9% in Bai Ku Yao, and 33.4%, 48.6% and 18.0% in Han (P > 0.05); respectively. There was no difference in the genotypic and allelic frequencies between males and females in the both ethnic groups. The subjects with AA genotype in Bai Ku Yao had higher serum TC levels than the subjects with GG and GA genotypes (P < 0.05). The participants with AA genotype in Han had lower serum HDL-C and ApoAI levels than the participants with GG and GA genotypes (P < 0.05 for each), but these results were found in males but not in females. Multivariate linear regression analysis showed that the levels of TC in Bai Ku Yao and HDL-C and ApoAI in male Han were correlated with genotypes (P < 0.05 for all). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, and blood pressure in both ethnic groups (P < 0.05-0.001).ConclusionThe present study suggests that the V825I polymorphism in the ABCA1 gene is associated with male serum HDL-C and ApoAI levels in the Han, and serum TC levels in the Bai Ku Yao populations. The difference in the association of V825I polymorphism and serum lipid levels between the two ethnic groups might partly result from different ABCA1 gene-enviromental interactions.

Background - Aim: In animal experiments, growth arrest-specific 6 (Gas6) protein plays a key role in the development of mesangial cell and glomerular hypertrophy in the early phase of diabetic nephropathy, and diabetic nephropathy is prevented by warfarin-induced inhibition of GAS6 protein. It was shown that GAS6 intron 8 c.834 + 7G > A polymorphism is protective against type 2 diabetes mellitus, and AA genotype is associated with higher blood levels of GAS6 protein. Our aim is to investigate whether this polymorphism is a risk factor for diabetic nephropathy in type 2 diabetes mellitus. Method: Eighty-seven patients with diabetic nephropathy were compared with 66 non-diabetic controls in terms of GAS6 intron 8 c.834 + 7G > A polymorphism. Patients with history of stroke, ischemic heart disease were excluded. Each patient was examined by the ophthalmologist to determine diabetic retinopathy. Results: Frequency of GG, GA and AA genotypes are similar in diabetic nephropathy and control groups according to GAS6 intron 8 c.834 + 7G > A polymorphism (p = 0.837). Rate of diabetic retinopathy was 54.02%. In the subgroup analysis, GA genotype was significantly more frequent than GG genotype in patients with diabetic retinopathy when compared to without diabetic retinopathy (p = 0.010). Conclusion: In our study, GAS6 intron 8 c.834 + 7G > A polymorphism was not associated with diabetic nephropathy in type 2 diabetes mellitus. However, heterozygous state of this polymorphism may be a risk factor for diabetic retinopathy in patients with diabetic nephropathy.

We investigated whether promoter -2518 single nucleotide polymorphism (SNP) of the monocyte chemoattractant protein-1 (MCP-1) gene contributes to susceptibility and clinical features or severity in Behçet's disease (BD) patients. One hundred and thirty-two BD patients and 113 healthy subjects, matched by sex and age, were enrolled. Promoter -2518 polymorphism of the MCP-1 gene was analyzed using automated sequencing. Clinical severity in BD patients was classified into mild, moderate, and severe features and assessed by total severity scores. Clinical features and severity was also compared according to genotypes using either the chi-squared or Fisher's exact test and Mann-Whitney test, as indicated. There were no significant differences in alleles (G allele vs. A allele, p=0.845) and genotypes with -2518 SNP (GG vs. GA vs. AA, p=0.916) between BD patients and controls. No clinical features were associated with genotypes with -2518 polymorphism of MCP-1. However, the frequency of either GA or AA genotype in patients with moderate lesions and moderate to severe lesions was significantly increased compared with that in patients with the GG genotype (p=0.044 and p=0.038, respectively). Total severity scores in the AA genotype were higher than those in the GG and GA genotypes (p=0.039 and p=0.003, respectively). Moreover, patients with either the GA or AA genotype had higher scores than those with the GG genotype (p=0.041). This study demonstrated that genotypes with A allele with -2518 polymorphism of the MCP-1 gene might have increased risk of severity of clinical features, but not susceptibility to BD.

Porcine beta-defensin-1 (PBD-1) gene plays an important role in the innate immunity of pigs. The peptide encoded by this gene is an antimicrobial peptide that has direct activity against a wide range of microbes. This peptide is involved in the co-creation of an antimicrobial barrier in the oral cavity of pigs. The objective of the present study was to detect polymorphisms, if any, in exon-1 and exon-2 regions of PBD-1 gene in Large White Yorkshire (LWY) and native Ankamali pigs of Kerala, India. Blood samples were collected from 100 pigs and genomic DNA was isolated using phenol chloroform method. The quantity of DNA was assessed in a spectrophotometer and quality by gel electrophoresis. Exon-1 and exon-2 regions of PBD-1 gene were amplified by polymerase chain reaction (PCR) and the products were subjected to single strand conformation polymorphism (SSCP) analysis. Subsequent silver staining of the polyacrylamide gels revealed three unique SSCP banding patterns in each of the two exons. The presence of single nucleotide polymorphisms (SNPs) was confirmed by nucleotide sequencing of the PCR products. A novel SNP was found in the 5′-UTR region of exon-1 and a SNP was detected in the mature peptide coding region of exon-2. In exon-1, the pooled population frequencies of GG, GT, and TT genotypes were 0.67, 0.30, and 0.03, respectively. GG genotype was predominant in both the breeds whereas TT genotype was not detected in LWY breed. Similarly, in exon-2, the pooled population frequencies of AA, AG, and GG genotypes were 0.50, 0.27, and 0.23, respectively. AA genotype was predominant in LWY pigs whereas GG genotype was predominant in native pigs. These results suggest that there exists a considerable genetic variation at PBD-1 locus and further association studies may help in development of a PCR based genotyping test to select pigs with better immunity.

BackgroundIt has been reported that dietary fats and genetic factors in individuals are associated with the pattern of fat distribution. This study aimed to evaluate the interaction between dietary fats intake and Caveolin1 (CAV-1) rs 3807s992 polymorphism with fat distribution in overweight and obese women.MethodsA total of 221 participants were included in the current cross-sectional study. Body composition, biochemical parameters were evaluated by body composition analyzer and Pars Azmoon kits and genotypes determination was performed by PCR–RFLP, dietary fats were measured using a validated semi-quantitative food frequency questionnaire (FAQ).ResultsThe frequency of GG, AA and AG genotypes were 53.1, 24.6, and 22.3%, respectively, and the mean intake of total dietary fat intake was 97.47 ± 36.87 g. There was positive significant interaction between total fat intake and AA genotype on visceral fat level (p = 0.001), trunk fat (p = 0.01) and waist circumference (p = 0.05), positive significant interaction between total fat intake and AG genotype on the waist to hip ratio (WHR) (p = 0.02) and visceral fat level (p = 0.05), positive borderline significant interaction between saturated fatty acid and AA genotype on the trunk fat (p = 0.06), and between trans-fatty acids and AG genotype on WHR (p = 0.04), visceral fat level (p = 0.01), and between monounsaturated fatty acid and AG genotype on WHR (p = 0.04), and a borderline interaction between polyunsaturated fatty acid and AA genotypes on visceral fat level (p = 0.06), negative significant interaction between AG genotypes and linolenic acid on WHR (p = 0.04), borderline significant interaction between ALA and AG genotype on WHR (p = 0.06).ConclusionsOur findings showed that CAV-1 rs 3807992 polymorphism and dietary fats were associated with fat distributions in individuals.

Aim: To investigate the influence of the polymorphic variants of CCND1 (G870A) and p73 (G4C14- to- A4T14) on the susceptibility to breast cancer development, also, to figure out their diagnostic and prognostic roles.Subjects and Methods: Blood samples were obtained from breast cancer patients and controls. Genotyping of CCND1 and p73 genes were carried out by PCR-RFLP and PCR-CTPP; respectively.Results: In comparison with the control group, CCND1 (G870A) GA and AA genotypes frequencies were significantly higher in breast cancer patients (p=0.035 and p=0.002; respectively), whereas CCND1 (G870A) GG genotype frequency was significantly lower (p&lt; 0.001). The CCND1 GA and AA genotypes significantly increased the risk for developing breast cancer compared with the GG genotype. The CCND1 (GA+AA) genotypes were significantly correlated with disease-free survival (DFS) of breast cancer patients. In comparison with the control group, p73 (G4C14/A4T14) GC/AT and AT/AT genotypes frequencies were significantly higher in breast cancer patients (p=0.013 and p=0.04; respectively), whereas p73 (G4C14/A4T14) GC/GC genotype frequency was significantly lower (p= 0.004). Â Compared with the GC/GC genotype, the p73 GC/AT and AT/AT genotypes significantly increased the risk for developing breast cancer. Beside being significantly correlated with DFS, p73 [(GC/AT)+ (AT/AT)] genotypes were indirectly correlated with tumor size, tumor pathological grade, patient's clinical stage, number of axillary lymph node involvement and Her2/neu expression.Conclusion: The GA and AA genotypes of CCND1 (G870A) polymorphism and the GC/AT and AT/AT genotypes of p73 (G4C14- to- A4T14) polymorphism can be used as diagnostic markers in breast cancer patients. The presence of the CCND1 (G870A) GA and AA genotypes and the GC/AT and AT/AT genotypes of p73 (G4C14- to- A4T14) polymorphism can increase the susceptibility to breast cancer incidence. Both of CCND1 (G870A) and p73 (G4C14- to- A4T14) polymorphisms can be used for prognosis of breast cancer patients.Â

To study the association of fat mass and obesity associated gene rs9930506 polymorphism with overweight and obesity in the Hazakh Children. PCR-restriction fragment length polymorphism was used to determine rs9930506 polymorphism in 118 patients with overweight or obesity and 141 controls. Serum lipid level including total cholesterol, triglyceride, high-density and low-density lipoprotein cholesterol, plasma glucose levels, and plasma insulin were monitored by using enzymatic method (Hitachi automatic clinical analyzer) and radioimmunoassay kit respectively. The genotype distributions of the control group and overweight or obesity group were in the Hardy-Weinberg equilibrium. The frequencies of AA, AG and GG were 0.458, 0.492 and 0.050 in the overweight or obesity group and 0.582, 0.397 and 0.021 in the controls respectively. There was no significant difference in frequencies of AA, AG and GG genotypes between control group and overweight or obesity group (χ(2) = 4.795, P = 0.091), but the frequency of GG + AG genotype in overweight or obesity group (0.542) was higher than that in the controls (0.418) giving significant difference (χ(2) = 3.957, P = 0.047). The frequencies of A allele were 0.703 in the overweight or obesity group and 0.780 in the controls respectively. There was significant difference in frequencies of A allele frequency between controls and overweight or obesity group (χ(2) = 3.986, P = 0.046). In the overweight or obesity group, the plasma glucose levels, BMI and hip circumference were (4.93 ± 0.52) mol/L, (79.70 ± 11.73) and (21.61 ± 2.72) cm in the persons with GG + AG genotype and (4.69 ± 0.56) mol/L, (75.28 ± 11.52) and (19.92 ± 1.98) cm in those of AA genotypes respectively. The plasma glucose levels, BMI and hip circumference of the persons with GG + AG genotype were higher than those of AA genotypes and the statistical significance was also observed (t = 2.430, P = 0.017; t = 2.053, P = 0.042; t = 3.891, P = 0.000). The present findings suggest that rs9930506 polymorphism on chromosome 16q12.2 may be associated with the development of overweight or obesity in the Hazakh Children, and the polymorphism may have some influence on serum glucose levels, BMI and hip circumference in this population.