Heterozygous GA Research Articles

Analysis of the association of interleukin 4 and interleukin 10 gene variants with basic personality traits

There is growing evidence that serum levels of various inflammation markers are associated with personality traits. However, only few studies investigated the link between genetic variants of cytokine encoding genes and psychological characteristics. In this study, we examined genotypes in 297 individuals to assess the association between common variants of interleukin 4 (IL-4) and interleukin 10 (IL-10) genes and basic personality traits of extraversion and neuroticism, measured using the Eysenck Personality Questionnaire (EPQ). We found that, in homozygous female carriers of high expression alleles Т (IL-4 C-589T) and G (IL-10 G-1082A), neuroticism scores were higher (p = 0.045 and p = 0.08, respectively). In turn, extraversion scores were significantly higher in both male and female carriers of heterozygous variants CT and GA (p = 0.01). Our results are in accordance with the behavioral immune system hypothesis, and the general paradigm on the role of personality traits in health and longevity.

Association of myeloperoxidase polymorphism (G463A) with cervix cancer.

Cervical cancer is the fourth most common cancer affecting women worldwide, according to the latest IARC release with 528 000 new cases every year. Infection by high-risk human papillomavirus (HPV) is necessary but not sufficient for progression to cancer. Epithelial tissues, the target of HPV infection, are heavily exposed to reactive oxygen species (ROS). Hypochlorous acid (HOCl) is a very potent ROS, and it is produced by myeloperoxidase (MPO). MPO, a lysosomal enzyme expressed in polymorphonuclear neutrophils (PMN), has the potential to kill HPV transformed cells, as a component of an intercellular induced-apoptosis pathway. This enzyme catalyzes the production of HOCl in the presence of hydrogen peroxide (H2O2). The H2O2 produced by the Doderlein's bacillus will interact with MPO, contributing to the intercellular induced-apoptosis pathway. We studied a functional polymorphism in the promoter region of MPO (G463A) and how it may affect the risk of developing cervix cancer. A sample of 100 patients with invasive cervical cancer and 122 control women were genotyped for MPO polymorphism by PCR-RFLP method. The statistical method used was χ(2). We found that women with the GG genotype had lower risk for cervical cancer than the women who displayed the heterozygous genotype GA (OR = 0.546, 95 % CI = 0.315-0.939, p = 0.028, OR = 2.210, 95 % CI = 1.257-3.886, p = 0.008, respectively). The genotype that leads to a higher concentration of ROS (GG) presents itself as a protection factor in comparison to the homozygous genotype (AA). This can be explained by the interaction of HOCl and superoxide of transformed cells that will generate apoptosis-inducing hydroxyl radicals.

Polymorphisms of Leptin (-2548 G/A) and Leptin Receptor (Q223R) Genes in Iranian Women with Breast Cancer.

Recent studies have shown that polymorphisms in leptin and leptin receptor genes are associated with increased risk for breast cancer. This study aimed at investigating -2548 G/A polymorphism in leptin gene and Q223R polymorphism in leptin receptor gene in patients with breast cancer. The study included 45 women with breast cancer and 41 healthy women. PCR-RFLP was used to determine the genotype of the subjects in terms of -2548 G/A polymorphism in leptin gene and Q223R polymorphism in leptin receptor gene. Serum levels of leptin were also measured by ELISA. For -2548 G/A polymorphism, the genotypes were homozygous AA (OR = 1.13; p = 0.8) and heterozygous GA (OR = 0.41; p = 0.2) and for Q223R polymorphism, the genotypes were homozygous RR (OR = 6.7; p = 0.09) and heterozygous QR (OR = 8.3; p = 0.06). The mean serum level of leptin was 33.22 ± 21.35 ng/mL in patients and 29.49 ± 23.27 ng/mL in the normal participants (p = 0.3). Although, despite the magnitude of the associations, the results suggested no statistically significant contribution of -2548 G/A polymorphism (in leptin gene), Q223R polymorphism (in leptin receptor gene), and serum leptin levels in predicting the risk of breast cancer, further studies with larger sample size are suggested.

The role of vitamin D in polycystic ovary syndrome

The role of vitamin D in polycystic ovary syndrome

Polymorphism of interleukin-17 and its relation to mineral density of bones in perimenopausal women.

BackgroundRecognition of different genetic variants underlying osteoporosis would make it possible to introduce individual, symptomatic treatment as well as early prophylaxis of osteoporosis.The aim of the study was to evaluate the frequency of the rs2275913 (−197G > A) polymorphism of the IL-17 gene and assess the relation of this polymorphism with the clinical parameters of the osseous turnover and degree of the postmenopausal osteoporosis.MethodsThe study included 800 women of postmenopausal (505) and reproductive (295) ages throughout the Wielkopolska region in Poland. The postmenopausal group included women with osteoporosis and osteopenia, and those who were healthy. Women at reproductive age were healthy. The frequency of the tested gene polymorphism was evaluated in the group where bone mineral density (BMD) was marked and in the control group.ResultsThe results obtained showed that the T-score in the female population with osteopenia was remarkably lower in women showing the GG genotype of -197G > A polymorphism of IL-17 gene compared to patients with heterozygous GA genotype. It has been shown that the BMD value for L2–L4 YA in the evaluated female population with osteoporosis is significantly higher in women with the GA genotype of -197G > A polymorphism of IL-17 gene compared to women with the GG genotype (76.32% versus 59.93%, P <0.05). It has also been noted that the BMD value for L2 to L4 AM in patients with the GG genotype was lower than in women with the AA genotype (69.73% versus 80.88%, P <0.05).ConclusionsIt is suggested that the -197G > A polymorphism of the IL-17 gene may be considered as a genetic factor of postmenopausal osteoporosis. This polymorphism can influence the bone mineral density and T-score value in young women and postmenopausal women.

SNPs in the exons of Toll-like receptors are associated with susceptibility to type 1 diabetes in Chinese population

ObjectiveToll-like receptors (TLRs) recognize a wide range of pathogen-associated molecular patterns (PAMP) and mount the initiation of immune response. Single nucleotide polymorphisms (SNPs) in exons of genes encoding TLRs might be responsible for the generation of an abnormal immune response which could lead to autoimmune diseases. In this study, we investigated the SNPs in TLRs in a Chinese population, and we hypothesized that SNPs in TLRs are associated with type 1 diabetes (T1D), an autoimmune disease caused by destruction of insulin producing pancreatic β-cells, in the studied population. Research design and methodsWe selected 28 SNPs in exons of TLRs with an aim to identify those that might have a direct correlation with T1D etiology and many have not been included in previous GWAS studies. Genotyping of those SNPs in TLRs was performed in 429 T1D patients and 300 age and gender-matched healthy controls in Chinese Han population which was not included in the earlier GWAS studies. ResultsAmong the SNPs genotyped, the T allele of TLR1–626 was positively associated with T1D (OR=1.98, Pc=0.01). We identified another T1D association locus in TLR6: the homozygous AA genotype of TLR6-1329 was negatively and heterozygous GA was positively associated with T1D (OR=0.54, Pc=0.02 and OR=1.70, Pc=0.03, respectively). We also identified the haplotype T-G-A in TLR1 gene to be positively associated with T1D (OR=2.22, Pc=0.03). Additional haplotypes in TLR-6 also showed significant positive and negative association. In addition, our haplotype analysis and conditional analysis showed that these two SNPs are the primary T1D associated loci among the SNPs tested in our cohort in each TLR gene. ConclusionSNPs and haplotypes in TLR1 and TLR6 gene were associated with T1D in Chinese Han population. Our study, for the first time, indicates that TLR1 and TLR6 gene might play important roles in the etiology of T1D.

Polymorphisms in the DNA repair gene ERCC2/XPD and breast cancer risk: a HapMap-based case-control study among Han Women in a Chinese less-developed area.

Genetic variations in DNA repair genes may impact repair functions, DNA damage, and breast cancer risk. This study is aimed to assess the associations of genetic polymorphisms in excision repair cross-complementing group 2 (ERCC2) with the risk of developing breast cancer. In total, 101 histopathologically confirmed breast cancer cases and 101 age/region-matched healthy controls were genotyped for rs 3916840, rs 1799793, and rs 238416 in ERCC2 by polymerase chain reaction-restriction fragment length polymorphism. The rs 238416 heterozygous GA genotype combined with the rs 238416 genotypes (GA+AA) showed a significant association with breast cancer susceptibility (corrected p<0.01, odds ratio [OR]=0.29, 95% confidence interval [CI]=0.15-0.54; corrected p<0.01, OR=0.31, 95% CI=0.17-0.56, respectively). The rs 238416 GA genotype carriers had a decreased risk of breast cancer. However, we observed no significant association between the rs 3916840 and rs 1799793 polymorphisms in ERCC2 and breast cancer risk. Moreover, haplotype analysis showed that the ACG haplotype was associated with a significantly decreased risk of breast cancer, whereas the GCG haplotype was associated with a significantly increased risk of breast cancer (corrected p=0.004 and p=0.002, respectively). Multifactor dimensionality reduction analysis demonstrated that the interactions between rs 3916840 and rs 238416 were significantly synergistic. To the best of our knowledge, this study is the first to demonstrate that the rs 238416 heterozygous genotype likely has a higher DNA repair capacity and, thus, can be protective against breast cancer in Chinese Han women.

Study of association between polymorphisms in the PSMB5 (rs11543947) and PSMA3 (rs2348071) genes and multiple sclerosis in Latvians

Functional realization of many signalling proteins and transcription factors implicated in the development and progression of multiple sclerosis is mediated by proteasomes. Aim of this case-control study was to evaluate genetic variations in the PSMB5 and PSMA3 genes encoding proteasomal subunits on the susceptibility to multiple sclerosis in Latvians. Methods. The rs11543947 (PSMB5) and rs2348071 (PSMA3) loci were genotyped in 291 multiple sclerosis patients and 305 healthy individuals and analysed general, subtype and sex-specific associations with the disease. Results. Loci rs11543947 and rs2348071 were identified as disease neutral and susceptible respectively. The rs2348071 heterozygous genotype GA showed strong main effect (P < 0.001; OR = = 1.891, 95 % CI [1.360–2.628]), and moderate (P < 0.01; OR = 1.663, 95 % CI [1.152– 2.402]) and strong (P < < 0.001; OR = 2.459, 95 % CI [1.534–3.943]) association with relapsing-remitting and secondary progressive phases of disease respectively. No genotype-sex interaction associated with multiple sclerosis has been detected. Conclusions. Our results suggest susceptibility of the rs2348071 heterozygous genotype to multiple sclerosis in Latvians.

Polymorphisms of leptin-b gene associated with growth traits in orange-spotted grouper (Epinephelus coioides).

In mammals, leptin has been demonstrated to perform important roles in many physiological activities and to influence development, growth, metabolism and reproduction. However, in fish, its function is still unclear. Duplicate leptin genes, leptin-a and leptin-b, have been identified in the orange-spotted grouper. In the present study, the polymorphisms in the leptin-b gene of the orange-spotted grouper were detected, and the relation between these polymorphisms and 12 growth traits were analyzed. Six polymorphisms (including 3 single nucleotide polymorphisms (c.14G>A, c.93A>G, c.149G>A) in exon 1, 2 SNPs (c.181A>G, c.193G>A) in intron 1, and 1 SNP (c.360C>T) in exon 2) were identified and genotyped from 200 different individuals. The results revealed that the SNP c.149G>A was significantly associated with growth traits, that the heterozygous mutation genotype GA having negative effects on growth traits. However, the other five SNPs (c.14G>A, c.93A>G, c.181A>G, c.193G>A, c.360C>T) did not show significant associations with all the growth traits. Compared with our findings in leptin-a gene, the results suggested that the leptin-a hormone has more important physiological effects in fish bodies than the leptin-b type. Moreover, leptin genes were supposed to be one class of major candidate genes of regulating growth traits in the orange-spotted grouper.

Thrombophilic Mutations as Risk Factor for Retinal Vein Occlusion

Retinal vein occlusion (RVO) is the second most common retinal vein disease and an important cause of blindness and visual morbidity. Many conditions are associated with RVO but the real role of the thrombophilic mutations is still unclear. To evaluate the potential role of thrombophilic mutations in RVO. We have evaluated 113 patients with RVO and compared with 104 volunteer controls. The controls were all healthy blood donors without previous venous thromboembolism episode or arterial thromboembolism episode. All patients were tested for 5 gene variants (here all named as mutations): factor V (FV) Leiden (G1691A), factor II (FII; G20210A), 5,1-methylenetetra-hydrofolate reductase (MTHFR; C677T), plasminogen activator inhibitor 1 (PAI-1; 4G/5G), and angiotensin-converting enzyme (ACE; Del/Ins). Statistical analysis were performed by the 2-tailed chi-square test. Statistical test showed that TT homozygous patients of the MTHFR C677T mutation (P = .017) and heterozygous GA patients of the FII G20210A mutation (P = .018) were significantly higher than that in controls. For FV Leiden, even if the values were higher in patients than in controls, P value was not statistically significant. Conversely, for the ACE (Ins/Del) and PAI-1 (4G/5G) mutations, no difference was observed among genotypes of patients with RVO and control participants. In our study, the FII G20210A and the MTHFR C677T mutations resulted significantly higher in patients than in controls; in contrast, thrombophilic mutation of FV, ACE, and PAI-1 genes was not statistically correlated with RVO. In spite of having found an association between some thrombophilic mutations and RVO, more studies with a major number of patients are necessary to determine the final role of these gene variants.

Prevalence of thrombophilic gene polymorphisms (FVL G1691A and MTHFR C677T) in patients with myocardial infarction

BackgroundInherited thrombophilia may be caused by mutations, polymorphisms in a variety of genes mainly involved in haemostatic pathways.Aim of the study, was to find the prevalence of thrombophilic gene factor V Leiden (FVL) and methylene tetrahydrofolate reductase (MTHFR) gene polymorphism in patients with myocardial infarction (MI), aiming at early diagnostic methods and guiding preventive procedures. Subjects and methodsThis study was carried on 30 patients who survived their first MI as compared to 15 healthy volunteers. Patients and controls were subjected to history, physical examination. Factor VL G1691A and MTHFR C677T genotypes were determined by RT PCR. ResultsThe prevalence of heterozygous FVL GA genotype was significantly higher among MI patients as compared to the control group. The prevalence of mutant homozygous AA was significantly higher in MI patients as compared to control. The low risk cases had a higher frequency of GA genotype as compared to high risk cases.As regards MTHFR C677T gene polymorphism, the prevalence of heterozygous MTHFR C677T CT genotype showed significant increase in MI patients compared with the control group. The prevalence of mutant homozygous TT genotype was significantly higher in MI patients as compared to the control group. The low risk cases had a higher frequency of heterozygous MTHFR C677T CT genotype than high risk cases. To concludeThe prevalence of heterozygous (FVL G1691A) and MTHFR C677T gene polymorphisms was significantly increased in MI patients compared with the control group and these gene polymorphisms are probably risk factors for myocardial infarction among Egyptian cases especially if integrated with other environmental and genetic risk factors. We recommended screening high risk patients for this polymorphism and the use of specific thromboprophylaxis to prevent recurrent thrombotic disease.

Systematic Review and Meta-Analysis of the Association between Complement Factor H I62V Polymorphism and Risk of Polypoidal Choroidal Vasculopathy in Asian Populations

PurposeTo investigate whether the polymorphism rs800292 (184G>A, I62V) in the complement factor H gene is associated with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD), in Asian populations.MethodsA comprehensive literature search was performed in PubMed, Medline, Web of Science, and reference lists. A system review and meta-analysis of the association between I62V and PCV and/or nAMD were performed from 8 studies involving 5,062 subjects. The following data from individual studies were extracted and analyzed: 1) comparison of I62V polymorphisms between PCV and controls; 2) comparison of I62V polymorphisms between PCV and nAMD. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. The Q-statistic test was used to assess heterogeneity, and Egger’s test was used to evaluate publication bias. Sensitivity analysis and cumulative meta-analysis were also performed.ResultsThe I62V polymorphism showed a significant summary OR1 for genotype GA+GG versus homozygous genotype AA was 3.18 (95% CI, 2.51–4.04, P<0.00001), the OR2 of heterozygous genotype GA versus AA was 2.29 (95% CI: 1.79–2.94, P<0.00001), the OR3 of homozygous genotype GG versus AA was 4.42 (95% CI: 3.45–5.67, P<0.00001), and the OR4 of allele G versus A was 2.04 (95% CI: 1.85–2.26, P<0.00001). Sensitivity analysis indicated the robustness of our findings, and evidence of publication bias was not observed in our meta-analysis. Cumulative meta-analysis revealed that the summary ORs were stable. There was no significant difference in every genetic model between PCV and nAMD (n = 5, OR1 = 0.92, OR2 = 0.96, OR3 = 0.90, OR4 = 0.94).ConclusionsOur analysis provides evidence that the I62V polymorphism is associated with an increased risk of PCV. The variant of I62V could be a promising genetic biomarker of PCV in Asian populations.

Genetic association of G896A polymorphism of TLR4 gene in leprosy through family-based and case-control study designs

Polymorphisms in TLR4 may change the function of the protein and alter the efficiency of immune response of host to infection. The high relevance of host gene polymorphisms with outcome of Mycobacterium leprae infection led us to study the genetic association of TLR4 G896A polymorphism in order to identify its risk among contacts of affected leprosy patients. For case-control study design a total of 628 individuals were recruited; 17 multicase leprosy families which included 32 case-parent trios were considered for family-based study. Genotyping was done using PCR-RFLP method. In case-control study AA genotype was positively associated while GA genotype was negatively associated with leprosy. In family based transmission disequilibrium test (TDT) analysis allele G was found to be over transmitted to the affected individuals. Case-control study suggests that homozygous AA genotype may confer susceptibility and heterozygous GA genotype may confer resistance to leprosy, while allele A was observed to increase risk and that of allele G may confer resistance to leprosy. No strong transmission disequilibrium was detected in family-based TDT analysis, possibly due to lower number of trios. In contrast to case-control data allele G was over transmitted to the affected ones in TDT analysis. To conclude, the frequencies of genotypes in household contacts were almost the same as in leprosy patients, suggesting that contacts with AA genotype may be at higher risk of leprosy and may therefore require prophylactic inputs.

Pathogenic variants screening in five non-obstructive azoospermia-associated genes

Non-obstructive azoospermia (NOA) is one of the most severe forms of male infertility and a recent, genome-wide association study (GWAS) has identified four risk loci associated with NOA. However, a large portion of the heritability of NOA has not been well explained by GWAS. By hypothesizing that rare, low-frequency and common genetic variants might point toward a causal relation between candidate genes and NOA, we performed a two-stage study including deep exon sequencing in 96 NOA cases and 96 healthy controls and a replication study in a larger population containing 522 NOA cases and 484 healthy controls. In the solexa sequencing stage, a total of two rare mutations (chr20. 1902132 and chr20. 1902301 in SIRPA), four common mutations (rs1048055 and rs2281807 in SIRPG, rs11046992 and rs146039840 in SOX5) were identified by using next generation sequencing (NGS). In the validation stage, subjects in the NOA group had a significantly decreased frequency of the heterozygous GA genotype in SIRPA (4.23%, 22 out of 520) than that in the control group (8.60%, 41 out of 477) [odds ratios (OR) 0.47, 95% confidence intervals (CI) 0.28-0.80] (P = 6.00 × 10(-3)). The rs1048055 in SIRPG was associated with a significantly increased risk of spermatogenic impairment, compared with the CC genotype (OR 3.93, 95% CI 1.59-9.70) (P = 3.00 × 10(-3)). Our study provides evidence of independent NOA risk alleles driven by variants in the protein-coding sequence of two of the genes (SIRPA and SIRPG) discovered by GWAS. Further investigation in larger populations and functional characterizations are needed to validate our findings.

Rs189037, a functional variant in ATM gene promoter, is associated with idiopathic nonobstructive azoospermia

To investigate the relationship between a functional variant rs189037(G>A) in ATM promoter and idiopathic nonobstructive azoospermia (INOA) in a Chinese population. Case-control study. Medical academy and hospital. Two hundred twenty-nine INOA patients and 236 fertile male controls. None. Genotyping was performed by polymerase chain reaction-based restriction fragment length polymorphism and subsequently confirmed by DNA sequencing. Odds ratio (ORs) and 95% confidence intervals (95% CIs) were calculated for the risk genotype and allele. Bioinformatic analysis was also performed to predict the biological function of rs189037(G>A). The AA genotype and A allele at rs189037(G>A) locus were both associated with an increased risk of INOA, with OR 1.90 (95% CI 1.214-3.007) for AA and 1.41 (95% CI 1.112-1.775) for A allele. The heterozygous GA and GA+AA had no relationship with INOA risk, with OR 1.06 (95% CI 0.761-1.472) and 1.28 (95% CI 0.954-1.708), respectively. Meanwhile, stratification by genotype showed that INOA patients with AA had higher FSH level, lower total T level, and smaller testicular size than those patients with GG. Furthermore, bioinformatic analysis predicted that the rs189037(G>A) variant was located in a well-conserved region in ATM promoter and that the transition of allele G to allele A might lead to differential allelic expression of ATM gene via modifying of the DNA-binding ability of transcription factor E2F1. The genetic variant rs189037(G>A) in ATM gene promoter contributes to an increased risk of INOA in a Chinese population, possibly through affecting the DNA-binding ability of E2F1 and subsequent ATM expression.

Population pharmacokinetics analysis of cyclophosphamide with genetic effects in patients undergoing hematopoietic stem cell transplantation

To build a population pharmacokinetic (PK) model of cyclophosphamide (CY) and its metabolite, 4-hydroxycyclophosphamide (HCY), in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) and to identify covariates, including genetic polymorphisms, which affect CY and HCY PK parameters. The study cohort comprised 21 patients undergoing HSCT who received CY intravenously between 2009 and 2011. Clinical characteristics and CY and HCY concentration data were collected for all patients, and ABCB1, ABCC2, GSTA1, GSTM1, GSTP1, GSTT1, CYP2B6, CYP2C19, and CYP3A5 genotyping was performed. A hypothetical enzyme compartment was conducted using the NONMEM program. A population PK analysis showed that the ABCC2 1249 genotype and aspartate aminotransferase levels significantly affected non-induced clearance (CL UI) and induced clearance (CL I) of CY, respectively. The final estimate of the mean CL UI and CL I of CY was 15.5 and 0.683L/h, respectively, and the mean volume of distribution (V 1) of CY was 88.0L. The inter-individual variability for CL UI, CL I, and V 1 of CY was 52.8, 200, and 18.0%, respectively. Additionally, the CL UI of CY was significantly decreased to approximately 51% in patients with the 1249 GA heterozygous genotype compared to those with the 1249 GG wild-type genotype (p < 0.05). There were only three heterozygous GA variants of ABCC2 1249 in the study patients. The population PK model developed in this study implies an influence of genetic factors on the clearance of CY. Clearance was moderately reduced in patients with the ABCC2 1249GA heterozygous genotype.

Lack of association between genetic polymorphisms in cytokine genes and tumor recurrence in patients with hepatocellular carcinoma undergoing transplantation

Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains one of the most common causes of poor long-term survival. However, the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated. The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC. Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes, i.e., the IL-1 family (IL-1alpha and IL-1beta), IL-6, IL-8, IL-10, TNF-alpha, and TGF-beta1, were genotyped in 93 HCC patients treated with LT using DNA sequencing. The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables. The genotype frequency of IL-10 -1082 A/G in patients with and without recurrence of HCC was AA 83.3%, GA 16.7% and AA 97.6%, GA 2.4%, respectively. The association between IL-10 -1082 GA and recurrence was significant (P=0.033). No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence. Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients (23.5 vs 5.7 months, P=0.001). However, multivariate analysis failed to reveal that the GA genotype of IL-10 -1082 A/G was an independent indicator of recurrence. This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population. The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.

Interleukin‐10 Gene Promoter and NFKB1 Promoter Insertion/Deletion Polymorphisms in Systemic Sclerosis

Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrotic, immunological and vascular abnormalities. Nuclear factor-kB (NFKB), as a key transcription factor involved in the regulation of immune responses, appears to be a good candidate for studies on the pathogenesis of autoimmune diseases, as well as the interleukin-10 (IL-10) polymorphism, which other studies have suggested an association with SSc. Our objective was to study the association of NFKB and IL-10 gene polymorphisms with SSc. One hundred and fifty-one SSc patients and 147 healthy bone marrow donors were enrolled in a case-control study. Blood was collected for DNA extraction; typing of IL-10 genes was made by polymerase chain reaction with sequence-specific primers (PCR-SSP), and NFKB gene typing was made by restriction fragment length polymorphism (RFLP). Patients underwent clinical evaluation, serology, Doppler echocardiography and chest high-resolution computed tomography. The frequency of IL-10 (-1082) GG genotype was found to be significantly higher in SSc patients (36.4%) as compared to healthy controls (22.4%) (P = 0.012). The frequency of heterozygous genotype GA was significantly lower (P = 0.004) in patients (38.4%) in comparison with control subjects (55.8%). A predominance of the high-producing IL-10 phenotype (GCC(+) /GCC(+) ) was observed in SSc patients compared with healthy controls (37.7% versus 24.5%, respectively; OR: 1.87, 95% CI: 1.10-3.19, P = 0.019). No significant difference was found in the allelic and genotype distribution of the NFKB promoter polymorphism between patients and controls. No statistically significant associations were found between IL-10 or NFKB polymorphisms clinical and laboratory features of SSc. Our results confirmed the association of the high-producing phenotype (GCC(+) /GCC(+) ) with increased risk for SSc, but found no correlation with NFKB polymorphisms.

Comparative distribution of Lysyl Oxidase (G473A) and NQO1 (C609T) polymorphism among tea-garden workers (habitual chewers of betel quid) of Darjeeling district and Kolkata city of West Bengal

Context:Chewing of processed arecanut products with tobacco and betel quid has been attributed to many oral pathological conditions. These products are very popular among the youngsters of lower economic groups. Genetic predisposition has been now identified as a major risk factor for increasing the susceptibility toward the disease among these chewers.Aims:Our study mainly aims to find out the predisposition of LOX (G473A) and NQO1 (C609T) polymorphisms and present a comparison between the population (habitually exposed to processed arecanut and smokeless tobacco products) of a metro-city Kolkata and the tea-garden workers of Darjeeling district of West Bengal.Settings and Design:Subjects for the study was recruited from various oral health check-up camps organized in the tea-gardens of Darjeeling district and Kolkata city.Materials and Methods:Genotyping analysis was done through a Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP)-based approach.Statistical Analysis Used:A two-way contingency table analysis software (JAVASTAT: http://statpages.org/ctab2 × 2.html) using 95% confidence interval was used to study the distribution of genotypes among the populations. A P < 0.05 was considered to be significant.Results:The results indicates both the heterozygous and homozygous carriers of NQO1 C > T (609) was found to be significantly higher among the north Bengal tea-garden workers [OR 0.480 (0.280-0.82) P = 0.01; 0.218 (0.091–0.524) P = 0.0001], respectively. Interestingly CT (21% in both) and TT (8% and 7%, respectively) were found to be equally distributed in the two populations. For LOX G > A (473) a significantly higher number of Kolkata individuals were found to carry the heterozygous GA allele in individuals aged <30 years [OR 3.779 (1.684-6.547) P = 0.001]. However, none were carrier of heterozygous GA allele of Kolkata population as compared with 29% north Bengal tea-garden workers aged above 31 years.Conclusions:A close observation of occurrence of oral diseases over time among such a population will be helpful to identify risk genotypes responsible for betel quid-induced oral diseases.

VEGF Polymorphisms in Gall Bladder Cancer

Purpose: Gall bladder cancer (GBC) is common in Chile and in north India. Angiogenesis plays an important role in carcinogenesis. Vascular endothelial growth factors (VEGF) at 6p12 play an important role in carcinogenesis. VEGF overexpression has been found in many cancers. We studied VEGF single nucleotide polymorphisms (SNPs) in GBC and gall stone associated benign diseases viz. chronic cholecystitis (CC) and xantho-granulomatous cholecystitis (XGC). Methods: DNA was extracted from blood in patients with GBC (n=195), CC (n=140), XGC (n=47), and normal controls (n=300). VEGF polymorphism (-1154G/A, -2578C/A, +936C/T and 18 bp -2549I/D) was investigated using PCR-RFLP method. Results: -1154G/A heterozygous genotype GA and +936C/T genotype TT were risk associated with GBC (OR 1.65, p=0.01; OR 2.59, p=0.02) and CC (OR 1.68, p=0.01; OR 3.48, p=0.003). -2578C/A heterozygous genotype CA was protective for GBC (OR=0.6, p=0.01). Combitorial analysis revealed that ICGC, DTGC, DCAC, and DTGA were predisposing haplotypes for GBC, CC, and XGC. Haplotype DTGA, containing mutant alleles, showed highest risk for GBC (OR 15.15, p<0.0001), CC (OR 7.5, p=0.007), and XGC (OR 10.6, p=0.001). Haplotype DCGC was risk protective for GBC (OR 0.28, p<0.0001), CC (OR 0.39, p<0.0001), and XGC (OR 0.32, p=0.001). Haplotype ICAC was protective for GBC (OR 0.27, p=0.0001). Conclusion: Hsing et al (2008) also found VEGF polymorphism to be associated with GBC. VEGF polymorphism may play a role in carcinogenesis of GBC and needs further evaluation.