Distribution Of CC Genotypes Research Articles

Genetic Analysis of Cytochrome P450 Polymorphisms in Drug-responsive and Drug-refractory Epileptic patients in Telangana

Aim: The present study aimed to evaluate the role of CYP2C9 and CYP2C19 genetic variations in drug-responsive/drug-refractory epilepsy, thereby facilitating the development of personalised drug strategies for effective treatment. Background: Cytochrome p450 was found to metabolize the drugs either by stimulation or by inhibition of cytochrome enzyme activity. CYP 450 genetic polymorphisms were postulated to influence the patient response to epileptic drugs by means of altered cytochrome enzyme activity resulting in varied therapeutic responses from patient to patient. Objective: The aim of the study is to evaluate the significance of CYP2C9 and CYP2C19 genetic variations in drug-responsive/drug-refractory epilepsy. Methods: A total of 65 subjects, 31 drug-refractory epilepsy cases and 34 drug-responsive epilepsy cases were included in the present study. The genetic analysis of CYP 450 2C9*2 (rs1799853), 2C9*3 (rs1057910), 2C19*2 (rs4244285) and 2C19*3 (rs4986893) polymorphisms was done by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism. Statistical analysis was performed by online Medcalc software to evaluate the association of CYP polymorphisms with drug-responsive/drug-refractory epilepsy cases. Results and Discussion: In the present study, a total of 31 drug-refractory epilepsy and 34 drug-responsive epilepsy patients were enrolled. The clinical parameters like duration of seizures was significantly different in drug-refractory cases (P=0.0001) and the postictal features were significantly associated with drug-refractory cases (p=0.0124). Regarding the genetic analysis, our study results for CYP2C9*2 (rs1799853:C>T) polymorphism did not show a significant association with the drug-refractory cases. The T allele frequency was 0.03 in epileptic drug-responsive cases and was found to be 0.0 in drug-refractory cases. Genotype distribution of CC, CT and TT was found to be 93.7%, 6.3% and 0% in drug-responsive cases and 100%, 0% and 0% in drug-refractory cases, respectively. The CYP2C9*3 (rs1057910) polymorphism C-allele was not observed in both drug-refractory and responsive cases in the present study. AA genotype (100%) was found in both drug-responsive and refractory cases. The study results for CYP2C19*2 (rs4244285) polymorphism did not show a significant association with the drug-refractory cases. The A allele frequency was 0.44 in epileptic drug-responsive cases and was found to be 0.45 in epileptic drug-refractory cases. Genotype distribution of GG, GA and AA was found to be 21.9%, 65.6% and 12.5% in drug-responsive cases and 20.83%, 70.84% and 8.33% in drug-refractory cases, respectively. The CYP2C19*3 (rs4986893) polymorphism did not show a significant association with the drug-refractory cases. The A allele frequency was 0.0 in epileptic drug-responsive cases and was found to be 0.0 in epileptic drug-refractory cases. Genotype distribution of GG, GA and AA was found to be 93.5%, 6.5% and 0% in drug-responsive cases and 100%, 0% and 0% in drug-refractory cases, respectively. Conclusion: In the present study, a significant difference was observed in the duration of seizures in the drug-refractory group and postictal features were significantly associated with the drug-refractory group. The genetic polymorphisms in CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3 did not show any significant association with drug refractory epilepsy. However, the study has to be extended to a large sample for the establishment of the significance of the specified polymorphisms in drug-responsive/drug-refractory epilepsy.

Associations between single-nucleotide polymorphisms of the interleukin-18 gene and breast cancer in Iraqi women.

According to long-term projections, by 2030, the world’s population is predicted to reach 7.5 billion individuals, and there will be roughly 27 million new cancer cases diagnosed. The global burden of breast cancer (BC) is expected to rise. According to the Ministry of Health-Iraqi Cancer Registry, cancer is the second largest cause of death after cardiovascular disease. This study investigated the interleukin-18 (IL18) single-nucleotide polymorphisms (SNPs) –607C/A rs1946518 and –137G/C rs187238 using the sequence-specific amplification-polymerase chain reaction approach. Regarding the position –607C/A, there was a highly significant difference between the observed and expected frequencies in patients and controls (χ2 = 3.16 and χ2 = 16.5), respectively. The AA and CA genotypes were associated with significantly increased BC risk (odds ratio [OR], 3.68; p = 0.004 and OR, 2.83; p = 0.04, respectively). Women with the A allele had a 5.03-fold increased susceptibility to BC. The C allele may be a protective allele against BC (OR, 0.19). Although position –137G/C showed no significant differences in the CC genotype distribution (p = 0.18), the frequency of the CC genotype was significantly higher in patients than in controls. In contrast, patients had a significantly higher frequency of GC genotypes than controls (p = 0.04), which was associated with an increased risk of developing BC (OR, 2.63). The G allele frequency was significantly lower in patients than in controls (55.0% vs. 76.2%, respectively). This SNP may be considered a common genotype in the Iraqi population, with the wild-type G allele having a protective function (OR, 0.19) and the mutant C allele having an environmental effect (OR, 2.63).

Interferon-induced transmembrane protein-3 rs12252-CC is associated with low differentiation and progression of hepatocellular carcinoma.

Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. The association between IFITM3 and hepatocellular carcinoma (HCC) has been reported. While the relationship between this genetic variation and the progress of HCC remains unclear. To address this issue, we explore the relationship between the IFITM3-rs12252 genetic variants and the progression of HCC in this study.A total of 336 candidates were enrolled in the study, including 156 patients with HBV related HCC and 180 patients with chronic Hepatitis B infections or liver cirrhosis. Liver cirrhosis or chronic hepatitis B were diagnosed with clinical characteristics and staging, laboratory testing, and imaging results of viral infection and hepatic damage. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3, and analyzed with the GraphPad Prism v 5.The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC as compared with the patients with chronic HBV infection or liver cirrhosis. Moreover, the distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Furthermore, the patients with CC genotype were found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes.This study indicates a correlation between the IFITM3-rs12252 CC genotype and the progression of HCC.

Association of Single-Nucleotide Polymorphisms of CD44 Gene with Susceptibility to Breast Cancer in Chinese Women.

BackgroundThis study aimed to evaluate the association of CD44 gene single-nucleotide polymorphisms with susceptibility to breast cancer.Material/MethodsThis case-control study included 242 breast cancer patients and 252 normal people without disease. The single-nucleotide polymorphisms of the CD44 gene in the 2 groups were genotyped by PCR-LDR method. The OR and its 95% CI was calculated by chi-square test and logistic regression analysis. The construction of haplotypes and their interaction analysis with relevant factors were carried out by SHEsis and SNPStats online.ResultsThe genotype distribution of CC and CT, CC and CC+CT, and CC+CT and TT in rs13347 showed a significant difference between cases and controls, and the difference in distribution of alleles C and T was statistically significant. The genotype and alleles distribution of rs4756195 and rs8193 showed no statistically significant difference (P>0.05). The haplotypes distribution of CAC, CGT, TAC, and TGT showed a significant difference between the 2 groups (P<0.05). The results of analysis of haplotypes and their interactions with relevant factors showed that breast cancer risk in the PR-negative group was significantly higher than that in the PR-positive group (P=0.016). We found an interaction between haplotypes and PR status.ConclusionsThe genotypes CT, CT+TT, TT, and allele T in rs13347 may be risk factors for breast cancer. The haplotype CAC may be a protective factor against breast cancer, and CGT, TAC, and TGT may be risk factors for breast cancer. The PR status interacts with CD44 gene SNP.

Correlations of pri-Let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer after transcatheter arterial chemoembolization

Background and aimSingle nucleotide polymorphisms (SNPs) within miRNAs could change their production or affinity with target genes, thus leading to malignant diseases. This study aims to explore correlations of pri-let-7 gene polymorphisms with the recurrence and metastasis of primary liver cancer (PLC) after a transcatheter arterial chemoembolization (TACE) surgical procedure. Materials and methodsA total of 302 PLC patients treated with hepatoprotective therapies after TACE were selected to and assigned into recurrent and non-recurrent groups. Genotypes of pri-let-7a-1 rs1073997 and pri-let-7a-2 rs629367 were analyzed by Taqman assay. The relationship between PLC with the mutation of each SNP was determined by a multivariate logistic regression analyses. Moreover, the association between survival and pri-let-7 gene polymorphisms was analyzed by the Kaplan-Meier method. The Progress Free Survival (PFS) curve, correlation of pri-let-7a-1 rs629367 with alcohol, HBsAg-positive and TNM III/IV were analyzed by a stratified analysis. Additionally, the risk factors for the recurrence of PLC were analyzed by a multivariate logistic regression analyses. ResultsResults showed that the allelic frequency of the pri-let-7a-2 rs629367 SNP in the recurrent group was higher than that of the non-recurrent group. The distribution of CC genotype was significantly higher than non-CC genotype in the recurrent group. Alcohol consumption, positive expression of hepatitis B surface antigen (HBsAg), AC + CC genotype of rs629367 and TNM III/IV were determined to be the risk factors for the recurrence and metastasis of PLC after TACE. We found a positive correlation between pri-let-7a-2 rs629367 with alcohol consumption, HBsAg-positive and TNM III/IV. The median PFS of HBsAg-positive and TNM III/IV patients with the AC + CC genotype of rs629367 was shorter than those with non-AC + CC genotype. ConclusionOur findings provide evidence that patients with PLC that carry the AC + CC genotype of pri-let-7a-2 rs629367 after TACE have a worse prognosis than those who carry the AA genotype. We speculate that the pri-let-7 rs629367 SNP could be used as a predictor of recurrence and metastasis after TACE for patients with PLC.

Calcitonin receptor gene polymorphisms at codon 447 in patients with osteoporosis and chronic periodontitis in South Indian population - An observational study.

Context:Chronic periodontitis and osteoporosis are multifactorial diseases which share common risk factors. Interactions between genetic and other factors determine the likely hood of osteoporotic fractures and chronic periodontitis. Calcitonin receptor (CTR) gene polymorphism is one of the important factors which contribute to the development of osteoporosis and chronic periodontitis.Aims:This study highlights the association of CTR gene polymorphisms at codon 447 in patients with osteoporosis and chronic periodontitis and healthy controls in south Indian population.Settings and Design:The study was designed as a case–control retrospective, observational clinical trial which was conducted to assess the role of CTR gene polymorphism in patients with osteoporosis and periodontitis as well as in healthy controls.Materials and Methods:A total of 50 subjects were taken into the study comprising of 20 healthy and 30 osteoporotic subjects with chronic periodontitis between the age group of 30–55 years. Within the limitations of our study, only 50 subjects were taken in the study due to the strict sampling method (Patients who were just diagnosed with osteoporosis and periodontitis and hence not taking any medication). 2 ml of blood sample was collected in ethylenediamine tetra acetic acid containing vials, and polymerase chain reaction was run to identify CTR gene polymorphism.Statistical Analysis Used:Statistical analysis was done by student t-test. Pertaining to C > T allele pattern there was a significant difference between the test and control group.Results:A significant difference was observed between the test and control group in relation to the C > T allele pattern. Patients showing TT genotype distribution had greater periodontal destruction and lower bone-mineral density compared to CT genotype distribution followed by CC genotype distribution indicating TT homozygotes are more prone to the development of osteoporosis with increased risk of fracture and loss of alveolar bone. Males and females showed equal susceptibility to osteoporosis and chronic periodontitis.Conclusions:CTR polymorphism at codon 447 may be associated with osteoporosis and chronic periodontitis

Assessment of the role of plasma nitric oxide levels, T-786C genetic polymorphism, and gene expression levels of endothelial nitric oxide synthase in the development of coronary artery disease.

Background:Reduced bioavailability of nitric oxide (NO) and the T-786C polymorphism of endothelial nitric oxide synthase (eNOS) gene have been reported as risk factors for the development of coronary artery disease (CAD) with conflicting results. We investigated the association of plasma NO levels, T-786C genetic polymorphism, and gene expression levels of eNOS with CAD risk in an Iranian subpopulation.Materials and Methods:Studied population included 100 patients with angiographically verified CAD and 100 ethnically matched controls. Analysis of T-786C genetic polymorphism and gene expression levels of eNOS was conducted by polymerase chain reaction (PCR) restriction fragment length polymorphism and real-time reverse transcription-PCR methods, respectively. Plasma levels of NO were measured using Griess method.Results:The CC genotype distribution (15% vs. 6%, P = 0.011) and minor C allele frequency (36.5% vs. 21.5%, P = 0.001) of eNOS T-786C polymorphism differed significantly between CAD patients and control. Furthermore, eNOS T-786C polymorphism was more common among smoker than nonsmoker CAD patients (27.7% vs. 7.8%, P = 0.044). The association of the eNOS T-786C polymorphism with the severity of CAD (number of diseased vessel) was significant (P < 0.05). The gene expression levels of eNOS were significantly lower in the heterozygote (0.49 ± 0.1, P = 0.023) and mutant homozygote (0.36 ± 0.09, P = 0.011) genotypes than that of wild-type genotype (P < 0.05). In addition, NO levels were significantly lower in CAD patients compared with control subjects (42.62 ± 12.26 vs. 55.48 ± 16.57, P = 0.002) and showed intergenotypic variation in the CAD patients.Conclusion:Our study indicated that reduced NO levels and eNOS T-786C genetic polymorphism are significant risk factors for the development and severity of CAD in the Iranian population.

Genetic polymorphism of antioxidant enzymes in eosinophilic and non-eosinophilic nasal polyposis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the paranasal sinuses, and its pathophysiology is not yet precisely known. It is suggested that oxygen free radicals play an important role in the pathogenesis of nasal polyposis. This study aimed to identify genetic polymorphisms of superoxide dismutase (SOD 2), catalase (CAT), and inducible nitric oxide synthase (iNOS) enzymes in eosinophilic CRSwNP and non-eosinophilic CRSwNP patients; the study also aimed to evaluate the effect of genetic polymorphism of antioxidant enzymes on CRSwNP etiopathogenesis. One hundred thirty patients, who received endoscopic sinus surgery due to CRSwNP, and 188 control individuals were included in this study. Nasal polyp tissues were divided into two groups histopathologically as eosinophilic CRSwNP and non-eosinophilic CRSwNP. Venous blood samples were taken from the patient and control groups. Polymorphisms in the Ala16Va1 gene, which is the most common variation of SOD-2 gene, and 21 A/T polymorphisms in catalase gene were evaluated with the restriction fragment length polymorphism method and -277 C/T polymorphism in the iNOS gene was evaluated with the DNA sequencing method. The GG genotype distribution for the (-277) A/G polymorphism in the iNOS gene was a statistically significant difference between eosinophilic CRSwNP and control groups (p<0.05). The CC genotype distribution for the SOD2 A16V (C/T) polymorphism was not statistically significant in all groups (p>0.05). The TT genotype distribution for the A/T polymorphism in catalase gene at position -21 was statistically significant differences in eosinophilic CRSwNP and control groups (p<0.05). Increased free oxygen radical levels, which are considered effective factors in the pathogenesis of CRSwNP, can occur due to genetic polymorphism of enzymes in the antioxidant system and genetic polymorphism of antioxidant enzymes in eosinophilic CRSwNP patients might contribute to the pathophysiology.

Association between polymorphisms of the HSPB7 gene and Cheyne–Stokes respiration with central sleep apnea in patients with dilated cardiomyopathy and congestive heart failure

BackgroundCSR-CSA is frequent in patients with CHF. Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background, yet one of the leading etiological causes of CHF. Studies have showed that the HSPB7 gene is associated with DCM. ObjectivesWe aimed to explore the prevalence of polymorphisms of the HSPB7 gene in the Chinese Han population with CSR-CSA and CHF caused by DCM. MethodsA total of 503 unrelated subjects of the Chinese Han population, including 283 CHF patients caused by DCM and 220 healthy controls, were involved in the study. The CHF patients were classified as the CSA-CHF group and the non-CSA-CHF group according to the PSG parameters. The rs1739843 polymorphisms of the HSPB7 gene were identified by real-time quantitative polymerase chain reaction. ResultsIn the present study, 35.8% of CHF patients caused by DCM had CSR-CSA. Comparison demonstrated that the CSA-CHF group had significantly higher TT genotype and T allele frequencies in the rs1739843 single nucleotide polymorphism (SNP) of the HSPB7 gene. There were no significant differences among the CC genotype distribution of the CSA-CHF group and the non-CSA-CHF group or the control group. ConclusionsThe rs1739843 polymorphism of the HSPB7 gene might be involved in the pathogenesis of CSR-CSA and CHF subjects caused by DCM in the Chinese Han population. This finding was from a genetic search for the role of the HSPB7 gene in CSR-CSA of CHF patients caused by DCM.

X-ray cross-complementing groups 1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility: A meta-analysis based on Chinese Han population.

X-ray cross-complementing groups 1 (XRCC1) rs1799782 C>T polymorphisms and colorectal cancer susceptibility were not clear. The purpose of this study was to evaluate the association between XRCC1 rs1799782 C>T polymorphisms and colorectal cancer susceptibility by meta-analysis. Related databases of Medline, CNKI, and Wanfang were systematic searched for the studies related to XRCC1 rs1799782 C>T polymorphisms and colorectal cancer risk in Chinese Han population. The genotype distribution of CC, CT and TT were extracted from each included studies in the colorectal cancer patients and healthy control subjects. The odds ratio (OR) and its 95% confidence interval (95% CI) was used to assess the correlation between genetype and colorectal cancer risk. The publications for this study was evaluated by Begg's funnel plot and Egger's line regression test. The median frequency of CC, CT, and TT genotype in cancer group were 48%, 41% and 11%; For control group, they were 51%, 40% and 8%; the pooled results showed that OR = 1.32 (95% CI: 1.041-1.67, P < 0.05). The pooled results indicated that XRCC1 rs1799782 C>T polymorphisms was associated with colorectal cancer susceptibility in recessive genetic model OR = 1.32 (95% CI: 1.041-1.67, P < 0.05), dominant genetic model OR = 1.21 (95% CI: 1.00-1.46, P < 0.05) and homozygous genetic model OR = 1.43 (95% CI: 1.07-1.91, P < 0.05). The funnel plot was significant asymmetric at the bottom and the Egger's test also indicated significant publication bias (t = 2.43, P = 0.04) for recessive genetic model. But, no publication bias was found in dominant and homozygous model (P > 0.05). Chinese Han people with rs1799782 TT/CT genotype of XRCC1 gene may have increased risk of developing colorectal.

Abstract 13440: The Asp358 A/C Polymorphism in Interleukin-6 Receptor Gene as a Novel Predictor of Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery in Chinese Han Population

Objective: Growing evidences suggest that genetic variation in inflammatory cytokines may play a key role in the development of postoperative atrial fibrillation (POAF). This study aimed to examine the association between three single-nucleotide polymorphisms in interleukin-6 receptor (IL-6R) gene Asp 358 A/C, IL-6 gene -174 G/C and -597 G/A and POAF following coronary artery bypass grafting (CABG). Methods: This prospective study enrolled 371 Chinese Han patients undergoing first time isolated CABG. The primary endpoint was the occurrence of POAF lasting ≥ 5mins. The patients were grouped as either POAF or non-POAF according to their ECGs, which were continuously monitored for the first 7 postoperative days. Genotypes for IL-6R gene Asp358 A/C, IL-6 gene -174 G/C and -597 G/A were determined. Multivariate logistic regression analysis was performed to identify independent risk factors for POAF. Results: Overall, 112 (30.2%) patients developed POAF. There was no significant difference in demographic and clinic data between the two groups, except that patients in the POAF group were significantly older than those in the non-POAF group (p &lt; 0.001), patients who had POAF appeared to have cerebrovascular disease more frequently than those who did not have POAF(p &lt; 0.05). Although frequencies of alleles and genotypes of IL-6 gene -174 G/C and -597 G/A polymorphism were similar in both groups, the CC genotype distribution and C allele frequencies of IL-6R gene Asp358 A/C were significantly higher in patients with POAF than those without POAF (p = 0.003). Univariate logistic analysis showed that the CC genotype for IL-6R gene Asp358 A/C, age, and history of cerebrovascular disease emerged as predictors of POAF. Multivariate analysis shows that the CC genotype for IL-6R gene Asp358 A/C and age were independent predictors of POAF. The adjusted (OR 2.06; 95% CI, 1.16 - 3.63; p = 0.01) of the CC genotype for IL-6R gene Asp358 A/C for predicting POAF was even greater than the unadjusted (OR 1.22; 95% CI, 1.01- 1.64; p = 0.04). Conclusions: This study suggests IL-6R gene Asp358 A/C polymorphism may contribute to the genetic susceptibility of POAF after CABG in Chinese Han population.

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer.

Polymorphisms in microRNA (miR) genes and their target sites are a distinct classification of variation in the human genome, which are rapidly being identified and investigated in human cancer. A polymorphism in the miR-196a-2 locus has demonstrated significant associations with various types of cancer, including lung, breast, esophageal and gastric tumors. However, miR-196a-2 has not been fully explored in ovarian cancer, which shares similar biological characteristics with other types of cancer. Therefore, the present study aimed to elucidate the association between a single nucleotide polymorphism (SNP) in the mature sequence of miR-196a-2 (rs11614913, T/C) and the clinical features of 479 Chinese patients with epithelial ovarian cancer (EOC). In addition, the biological significance of this polymorphism was investigated in the OVCAR3 ovarian cancer cell line. Risk association was evaluated in 479 cases of EOC patients and 431 controls. SNPs were analyzed by using polymerase chain reaction based restriction fragment length polymorphism assay. miR-196a expression was evaluated with reverse transcription polymerase chain reaction. The influence of miR-196a-2 rs11614913 T/C on EOC cell migration and invasion ability was further investigated in vitro. The results revealed significant differences in the homozygous CC genotype distribution in patients with EOC (n=479), compared with that of the control subjects (n=431; P=0.026). Analysis of the association between genotype and the risk of EOC revealed that individuals who carried the homozygous CC genotype were 1.34-fold more susceptible to EOC, compared with those carrying the wild-type TT and heterozygous CT genotypes [odds ratio, 1.34; 95% confidence interval, 1.04-2.17; P=0.023]. In addition, the role of this polymorphism in the production of mature miR-196a was investigated. Significantly enhanced production of mature miR-196a was revealed in the C-allelic compared with that of the T-allelic miR-196a-2 precursor (P<0.05). Further examination indicated that miR-196a significantly promoted cell migration and invasion ability in the human OVCAR3 ovarian cell line (P<0.05). In conclusion, the results indicated that the miR-196a-2 rs11614913 CC genotype may increase the risks of ovarian cancer by affecting the expression of mature miR-196a and enhancing cell migration/invasion. The current results provided evidence that the T>C polymorphism in the miR-196a-2 precursor may influence tumorigenesis and metastasis in EOC, and suggested that the functional SNP rs11614913 in the promoter region of pri-miR-196a-2 may be a potential indicator of EOC susceptibility in the population analyzed.

The -137G/C single nucleotide polymorphism in IL-18 gene promoter contributes to tuberculosis susceptibility in Chinese Han population

BackgroundInterleukin (IL) -18 is crucial to host defense against mycobacterial infections. Recent studies have indicated IL-18 gene polymorphisms are associated with susceptibility to several clinical diseases. ObjectiveThe aim of this study is to investigate the association of IL-18 (-137G/C and -607C/A) gene promoter single nucleotide polymorphisms (SNPs) with susceptibility to tuberculosis (TB), and the effects of those SNPs to its protein producing capacity in Chinese Han population. Methods407 TB patients (including 113 children and 294 adults) and 469 healthy volunteers (including 167 children and 302 adults) from Chinese Han population were enrolled. The IL-18 gene promoter polymorphisms at positions of −137 and −607 were determined by sequence specific primer-polymerase chain reaction (SSP-PCR). The IL-18 levels in the supernatants of PBMCs from 46 healthy volunteers were measured by ELISA. ResultsThe gene distribution of IL-18 -137G/C and -607C/A showed none difference between adult and pediatric population. The frequency of IL-18 -137GG genotype was significantly higher in total TB group than that in total healthy control group (79.1% V 69.3%, P<0.01), while the frequencies of GC genotype and C allele were conversely lower (19.2% V 27.9%, P<0.01; 11.3% V 16.7%, P<0.01 respectively). The difference of the -137CC genotype distribution between patients and controls was not observed. At the -607C/A polymorphic site, patient and control groups had a very similar gene distribution. Isolated PBMCs with IL-18 -137GC/CC genotype were able to produce a higher level of IL-18 than those with IL-18 -137GG genotype, either spontaneously or in response to PMA plus calcimycin A23187. ConclusionIL-18 -137G/C polymorphism contributed to TB susceptibility in Chinese Han population. Allele G might be a predisposing gene of TB, while allele C probably plays a role in preventing mycobacterium tuberculosis infection by promoting more vigorous protein expression.

ABCB1 C3435T polymorphism is associated with susceptibility to major depression, but not with a clinical response to citalopram in a Turkish population

BackgroundThe ATP-binding cassette sub-family B member 1 (ABCB1) gene, which encodes the p-glycoprotein at the blood–brain barrier, is investigated for patients’ susceptibility to major depressive disorder (MDD) and their therapeutic response to antidepressants. However, there is an inconsistency between the studies of different ethnic groups. The current study aimed to determine the potential correlations of the ABCB1 gene C3435T polymorphism with the susceptibility to MDD and the therapeutic response to citalopram in a Turkish population. MethodsFifty-four patients with MDD who received citalopram and 70 controls from the Turkish population were genotyped for ABCB1 C3435T polymorphism. To assess the therapeutic response to citalopram, all patients were rated baseline, first, second, fourth and sixth weeks according to the 17-item Hamilton Rating Scale for Depression (HAMD-17). ResultsThere was a significant correlation between the patient and control groups for ABCB1 C3435T polymorphism. Distribution of CC genotype and C allele frequency were higher in the patients than in the control group (p=0.006, p=0.020, respectively). However, no correlation between ABCB1 C3435T polymorphism and a therapeutic response to citalopram was observed. ConclusionOur results suggested that C3435T polymorphism in the ABCB1 gene may be an indicator of the susceptibility to major depression, without a likely treatment response to citalopram in a Turkish population. These findings should be replicated in studies on larger patient groups with different ethnicities.

SPP1 gene polymorphisms associated with nephrolithiasis in Turkish pediatric patients.

To investigate the association between SPP1 gene polymorphisms and nephrolithiasis. A total of 65 pediatric patients and 50 healthy controls were enrolled in this study. Two known polymorphisms of the SPP1 gene, c.240T > C and c.708C > T nucleotide substitutions, both of which were also known as synonymous aminoacid polymorphisms, D80D and A236A, respectively, at SPP1 gene cDNA level were investigated. SPP1 gene polymorphism was evaluated using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. In c.240T > C polymorphism, C allele frequency [Odds Ratio (OR), 2.13; 95% Confidence Interval (CI), 1.170 to 3.880; P = .013] and CC genotype distribution (OR, 2.946; 95% CI, 0.832 to 10.431; P = .094) and in c.708C > T polymorphism, T allele frequency (OR, 2.183; 95% CI, 1.197 to 3.980; P = .011) and TT genotype distribution (OR, 3.056; 95% CI, 0.861 to 10.839; P = .084) were found to be higher in the patient group. SPP1 polymorphisms were found to be associated with nephrolithiasis and it may be suggested that SPP1 gene polymorphism could be a useful marker for evaluation of the early genetic risk factor in childhood nephrolithiasis.

IL28B Genotype Does Not Correlate with HIV Control in African Americans

HIV-1 natural viral suppressors (NVS) are individuals that control HIV replication without antiretrovirals (also know as HIV elite controllers). We have recently shown that these individuals have an elevated rate of hepatitis C virus (HCV) clearance. Given the association of IL28B genotype, specifically the rs12979860 single nucleotide polymorphism (SNP) based CC genotype, with HCV clearance, we studied its association with HIV control in 172 African American HIV subjects and 173 race-matched controls. The frequency of the CC genotype was 12.5% in the NVS, 14.7% in the LVL ("low viral load" cohort with 400-20,000 HIV-1 RNA copies/mL), 17.8% in the MHVL ("medium/high viral load" cohort with >20,000 HIV-1 RNA copies/mL), and 11.6% in an HIV-negative cohort. There was no statistical significance in the CC genotype distribution between these cohorts (p= 0.48 between the NVS and non-NVS HIV positive controls, p= 0.85 between NVS and HIV-negatives). We also did not observe any association between CC genotype distribution and HIV RNA viral load, as a continuous measure. The IL28B CC genotype does not account for the noted HIV control in our specific NVS cohort. Further studies will be needed to determine if a common genetic factor can primarily account for any joint clearance of HCV and control of HIV.

The COL5A1 Gene

Running economy, a key component of endurance ability, has been shown to be associated with flexibility. Increased stiffness (inflexibility) may improve running economy and therefore endurance running ability. The COL5A1 gene, which encodes the α1-chain of type V collagen, was found to associate with measures of flexibility. Type V collagen is a quantitatively minor fibrillar collagen, which is believed to regulate fibrillogenesis within tendons and other connective tissue. The aim of this study was therefore to determine whether the COL5A1 gene is associated with endurance performance. Three hundred thirteen Caucasian male participants who completed either the 2006 or the 2007 226-km South African Ironman triathlon (3.8-km swim, 180-km bike, and 42.2-km run) participated in this study. All participants were genotyped for the COL5A1 BstUI restriction fragment length polymorphism (RFLP). The COL5A1 BstUI RFLP was significantly associated with time to complete the running component of the triathlon. Participants with a TT genotype completed the running component of the race significantly faster than individuals with a CC genotype (P = 0.019; mean ± SD: TT = 294.2 ± 52.1 min, CC = 307.4 ± 48.6 min). In addition, there was a significant linear trend (P = 0.020) in the CC genotype distribution when the run times were divided into the fastest (13%), middle (17%), and slowest (25%) tertiles. There were no significant genotype differences for time to complete the swim, the bike, or the overall race. COL5A1 BstUI RFLP, body mass index, age, and 15 wk of running training history predicted 30% of the variance in running performance. This is the first study to identify the COL5A1 BstUI RFLP as a marker for endurance running performance. Further studies are required to replicate these findings.

Investigation of interleukin-13 gene polymorphisms in individuals with chronic and generalized aggressive periodontitis in a Taiwanese (Chinese) population

The interleukin-13 (IL-13) -1112 C/T polymorphisms have been analyzed previously in a North European population of patients with aggressive periodontitis. The present study was carried out to investigate the association of polymorphisms in the IL-13 gene with susceptibility to periodontitis in a Taiwanese population. The genotyping of IL-13 -1112 C/T polymorphisms in 60 patients with aggressive periodontitis, 204 patients with chronic periodontitis and 95 healthy controls was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Genotypes and allele frequencies among study groups were compared using Fisher's exact test (p < 0.05). Pearson's chi-square test was used for analysis of the Hardy-Weinberg equilibrium. The distributions of CC genotypes and C alleles between patients with aggressive periodontitis and healthy controls were significantly different (p = 0.034 and 0.046). After adjustment for age, gender, betel nut chewing and smoking status using logistic regression analysis, the odds ratio (OR) was 6.45 [95% confidence interval (CI) = 1.99-23.72, p = 0.003] for aggressive periodontitis. However, the CC genotype was only significantly associated with the risk of aggressive periodontitis in the nonsmoking group (OR = 4.48, 95% CI = 1.31-16.93, p = 0.020). The CC genotype or C allele appears to increase the risk of developing aggressive periodontitis in Taiwanese subjects.

Association of ABCB1 and NR1I2 polymorphisms with response to carbamazepine in Malaysian epilepsy patients

The human nuclear pregnane X receptor (PXR;NR1I2) which regulates the expression of ABCB1 gene which encodes phosphoglycoprotein, an efflux pump for carbamazepine (CBZ). The aim of this study was to investigate whether ABCB1 C3435T and NR1I2 A7635G variants significantly impact the response of epilepsy patients to CBZ monotherapy. ABCB1 C3435T and NR1I2 A7635G genotyping were performed on 168 Malaysian epilepsy subjects (76 drug‐responsive and 92 drug‐resistant) receiving CBZ monotherapy by PCR‐RFLP. The results for C3435T revealed a genotype distribution of CC, CT, TT: 39.5%, 43.4%, 17.1% for drug‐resistant patients compared to CC, CT, TT: 29.3%, 58.7%, 12.0% for drug‐responsive patients. The genotypes distribution of A7635G in the drug‐resistant patients for AA, AG, and GG were 13.0%, 39.1%, 47.8% and in drug‐responsive patients 10.5%, 57.9%, 31.6%, respectively. Furthermore, among drug‐resistants and drug‐responsive patients, the frequency of carriers of T allele and was 41.3.1% and 38.8% and for G allele 67.4% and 60.5%, respectively. The association of genotype and allele frequencies in C3435T and A7635G with response to CBZ was nonsignificant. In conclusion, the allelic and genotype analysis in Malaysian epilepsy patients suggests that the NR1I2 A7635G and ABCB1 C3435T polymorphisms are not associated with resistance to CBZ.

Study on the relationship between HBV infection and polymorphism of CIITA G-944C gene among Jinuo, Dai and Aini minority populations in Yunnan province

To explore the relationship between HBV infection and the genotypes and allele frequencies of CIITA G-944C gene polymorphism in three minority populations (Jinuo, Dai and Aini population) in Xishuangbanna district, Yunnan province. Polymerase chain reaction and sequencing method were used to study the genotypes and allele frequencies distributions of CIITA G-944C gene polymorphism in those three populations. Relationship between the genotypes distribution and HBV infection results were also analyzed. The rates on HBV infection and HBsAg carrier status in Aini minority population were 89.2% and 16.3%, which were significantly higher than in Jinuo (27.9% and 3.9%, χ(2) = 135.196 and 10.361, P = 0.000 and 0.001) and Dai population (44.9% and 6.6%, χ(2) = 96.783 and 8.748, P = 0.000 and 0.003) while among Aini population it was significantly different with the other two minority populations. The CC genotype and C allele frequencies were more distributed in Aini population than in the other two minority populations. In contrast, the GG genotype and G allele frequencies were lower than the other two minority populations, with χ(2) rates between Aini and Jinuo population were 11.841 and 12.208 and the P as 0.003 and 0.000 respectively while the χ(2) rates between Aini and Dai population were 23.902 and 20.220 with P value as 0.000 and 0.000. The genotypes frequencies of CIITA G-944C was significantly different in the infected individuals (IF) group and health control (HC) group in Jinuo population (χ(2) = 6.150 and 4.911, P = 0.046 and 0.027). When compared with HBsAg(+) group and HBsAg(-) group, the genotypes and allele frequencies were different in Aini population and the total three minority populations (χ(2) rates in Jinuo minority were 8.650 and 5.034 with P values as 0.013 and 0.025). However, the χ(2) rates in the whole population were 13.047 and 9.416 with P values as 0.001 and 0.002, respectively. The distribution of CC genotype and C allele gene in HBsAg(+) group was increasing. Data from non-condition logistic regression analysis and adjusting for confounding factors, the HBsAg(+) group had a significantly increase of HBsAg(-) group under the C allele Recessive Model (P = 0.000; OR = 2.964; 95%CI: 1.609 - 5.460). The genotypes and allele frequencies distribution of CIITA G-944C were different in the three ethnic populations. Polymorphism of this gene was closely associated with HBsAg carrier. The CC genotype patients were more easily to become HBsAg carrier.