Studied Single Nucleotide Polymorphism Research Articles

(087) Association of ESRα T397C (rs2234693) with Male Infertility: A Meta-analysis

Abstract Introduction Infertility is the incapability to achieve fertilization after a certain period following sexual intercourse without any contraceptive measures which affects 1 in 6 couples. Male factors contribute 50%. The male reproductive system is affected by both environmental and genetic factors. Genetics variations include chromosomal aberrations, genomic and/or mitochondrial single gene mutations or polymorphism, and multiple gene mutations or polymorphism that result in spermatogenic failure. Genetic variations of key genes might have a role in male infertility. In this regard, polymorphism in the estrogen receptor gene may be an important factor increasing the risk of male infertility. In men, estrogen is produced in the testis by Sertoli cell, Leydig cell and germ cells that play an important role in the maturation and capacitation of sperms. The action of estrogen is mediated by two specific Receptors: Estrogen receptors α (ESRα) and Estrogen receptor β (ESRβ). ESRα gene is present on chromosome 6q25. It consists of 8 exons which are parted by 7 intronic regions having a complete size of 140 kb. ESRα codes for 595 amino acid proteins. The most widely studied single nucleotide polymorphism (SNP) in ESRα is T397C (rs2234693). It is found in intron 1 and divided by 46 bp. Few previously published studies reported an association between this SNP in ESRα and male infertility, while others found no association. Objective The present study aims to estimate the association between ESRα T397C (rs2234693) and male infertility. Methods PUBMED, CENTRAL, Google Scholar and PMC articles were searched, whereas case-control, published studies regarding ESRα T397C (rs2234693) and male infertility were selected for this meta-analysis. Results Four studies finally fulfilled the criteria of the meta-analysis. No significant association (p > 0.05) was found overall, between ER alpha polymorphism and male infertility, based on all of the four genetic models. However, when stratified into two ethnic groups, ER polymorphism was found to be significantly associated with male infertility in the Caucasian group based on the dominant model (CC + CT vs TT: OR= 1.43, 95% CI [1.08-1.91], I2 = 89%) as well as recessive model (CC vs CT+TT: OR= 1.34, 95% CI [1.01-1.76], I2 = 0%), whereas, in the Asian group, only the dominant model (CC + CT vs TT: OR= 1.97, 95% CI [1.58-2.46], I2 = 98%) indicated significant association of ER alpha polymorphism with male infertility. Conclusions ESRα T397C (rs2234693) polymorphism is linked with male infertility in the two ethnic groups, i.e., homozygous conditions in Caucasian and dominant conditions in Asian populations. Disclosure No

PCR-RFLP genotyping analysis of TP53 Arg72Pro polymorphism and susceptibility to esophageal cancer in Pakistani population

Background and objectiveTumor suppressor gene TP53 is necessary for prevention of inappropriate cell proliferation and maintenance of genome integrity. TP53 Arg72Pro is the most studied single nucleotide polymorphism (SNP) associated with different cancers including esophageal cancer (EC). The study was established to investigate relationship between Arg72Pro polymorphism and EC susceptibility. Materials and methodsDNA from a total of 200 individuals (100 EC patients and 100 controls) were genotyped for TP53 codon 72 (Arg72Pro) polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was used to estimate odds ratios and 95% confidence interval. ResultsSignificant differences in genotypes of Arg72Pro polymorphism between cases and controls were observed (P < 0.05). The patients represented 34% Pro/Pro, 44% Arg/Pro and 22% Arg/Arg whereas controls had 19% Pro/Pro, 42% Arg/Pro and 39% Arg/Arg genotypes. Pro/Pro variant showed 3.17-fold (95% CI: 1.47–6.83, P = 0.003) and Arg/Pro 1.71-fold (95% CI: 0.85–3.45, P = 0.071) increased EC risk compared with Arg/Arg. The Pro/Pro genotype was found to be significantly, whereas Arg/Pro was non-significantly associated with the esophageal cancer risk. Both males and females with Pro/Pro genotype were highly susceptible to cancer. Preserved meat consumers with Pro/Pro genotype were 4.8 fold (95% CI: 1.7–13.8) and subjects aged >50 with Pro/Pro were 4.6 fold (95% CI: 1.8–11.8) at increased risk of esophageal cancer. ConclusionsOur study suggests that Pro72 variant of TP53 polymorphism is highly correlated with increased EC. Further, the interaction between this polymorphism and tobacco consumption significantly affected EC development in Pakistani population.

Affective Language, Interpretation Bias and Its Molecular Genetic Variations: Exploring the Relationship Between Genetic Variations of the OXTR Gene (rs53576 and rs2268498) and the Emotional Evaluation of Words Related to the Self or the Other.

Several studies have demonstrated links between oxytocin and socio-emotional information processing. Regarding the frequently studied single nucleotide polymorphism (SNP) rs53576 and the less studied, functional polymorphism rs2268498 of the oxytocin receptor (OXTR) gene, previous research suggested that their variants might be associated with different proficiency in the processing of social information. Differences between the genotype variants are not restricted to non-verbal stimulus processing but have also been reported in the verbal domain. Moreover, there is evidence that oxytocin expression influences empathic communication and language development during childhood, indicating that language-based theory-of-mind abilities may be affected by interindividual differences in OXTR genotypes as well. The present study therefore investigates whether two prominent SNPs of the OXTR gene (rs53576 GG vs. A+; rs2268498 TT vs. C+) also play a role in the affective evaluation of verbal stimuli varying in emotional valence and in self-other reference. Participants (N = 149 Caucasian participants, 104 females; A+: n = 80, GG: n = 69; C+: n = 98, TT: n = 51) were presented a series of written, self-, other-, and unreferenced words of positive, negative, and neutral valence and asked to affectively evaluate each word pair as positive, negative, or neutral by button press. In line with previous research, reaction times and accuracy (number of valence-congruent responses) showed a self-positivity bias (i.e., preferential processing of self-related positive words), which, however, was unaffected by participants’ genotype. Regarding affective evaluation of neutral words (interpretation bias), A+ carriers displayed a weaker positive interpretation bias compared to GG carriers in the other– and unreferenced stimulus categories. C+ carriers showed a weaker positive interpretation bias than TT carriers in the self-reference condition and in the other-reference condition. These effects were independent from participants’ gender. The present results suggest that the OXTR genotype and hence participants’ genetic oxytocin sensitivity may cause an interpretation bias in the spontaneous appraisal of neutral words.

Pharmacogenetic Correlates of Antipsychotic-Induced Weight Gain in the Chinese Population.

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that >25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.

IL-37 gene variant (rs3811047): A marker of disease activity in rheumatoid arthritis: A pilot study

Background: Rheumatoid arthritis (RA) is a joint destructive disorder with great morbidity. Unraveling genetic determinants causing the disease would pave the road towards early detection and precise medicine. Interleukin 37 (IL-37), a natural inhibitor of innate immunity, was shown to be a key modulator in RA. Plasma levels were deregulated and correlated with disease activity. Therefore, we hypothesized the IL-37 gene variants could influence the clinical characteristics of RA patients.Objective: This is a pilot study to assess the association of rs3811047 variant of IL-37 gene with RA development and disease activity in an Egyptian population.Methods: A total of 100 individuals (50 RA patients and 50 healthy individuals) were enrolled in the study. Disease activity score of 28 joints (DAS28) was estimated for RA patients. Genotyping was performed using Real-Time PCR technology.Results: There was no statistically significant association between genotype frequencies of rs3811047 and RA risk. However, there was a significant relationship between the studied single nucleotide polymorphism (SNP) and disease activity. Patients carrying the GG genotype had higher DAS28 score than patients with AA or AG genotypes (p = .041).Conclusion: IL-37 gene rs3811047 SNP was associated with more severe RA disease activity in the current population. Larger epidemiological study is warranted to validate our results.

Study of the association of Trp64Arg mutation of beta three adrenergic receptor with obesity in Saudi population

Introduction: Beta three adrenergic receptor (ADRB3) is an adrenergic receptor that induces activation of adenylate cyclase located mainly in adipose tissue and is involved in the thermogenesis of brown fat tissue and in the regulation of lipolysis. Agonists of ADRB3 are found to induce the thermogenesis process of human brown fat tissue and thus believed to be excellent anti-obesity targets. The most studied single nucleotide polymorphism (SNP) of ADRB3 is rs4994. Inconsistent findings have been found in earlier studies about the association of rs4994 polymorphisms with obesity among different populations. The association of ADRB3/rs4994 polymorphism with obesity among the Saudi population is unknown. This study aimed to investigate the association of ADRB3/rs4994 polymorphism with obesity, blood lipids and blood pressure in the Saudi population.&#x0D; Method: This study was a case control study involving 88 obese healthy volunteers and 84 non-obese (controls) volunteers recruited from the King Khaled University Hospital (KKUH), Riyadh City, Saudi Arabia. Using KASPTM (Competitive Allele-Specific PCR) the rs4994 genotype for each participant was determined. The frequency, distribution, and association of each genotype with body mass index (BMI) and lipid profile were calculated.&#x0D; Results: The distribution of CC, TT and CT genotypes in the study population was 0.37, 0.06 and 0.56, respectively. The heterozygote CT genotype was associated with a reduced risk of obesity (odds ratio (OR)=0.4398, 95%CI=0.2338 to 0.8277, P-value=0.010). It was more frequent in the non-obese participants compared to the obese participants (67.9% vs. 44.3%, respectively). Moreover, participants with the CT genotype had a significantly lower BMI (P=0.004). In contrast, the CC genotype was associated with an increased risk of obesity (OR=2.5, 95%CI=1.3467 to 4.8758, P-value=0.004). The frequency of the CC genotype was higher in obese participants compared to the non-obese ones (46.6% vs. 28.6%, respectively). Participants with the CC genotype demonstrated a significantly higher BMI than participants with the CT or TT genotypes (Q= 4.5, P=0.004). The TT genotype had no significant effects on the participants’ BMI (OR=2.9, 95%CI=0.7563 to 11.5759, P value=0.11), and it was higher in obese compared to non-obese participants (9.1% vs. 3.6%, respectively). No significant effect of ADRB3/rs4994 polymorphism on blood lipid profile or blood pressure was observed.&#x0D; Conclusion: The findings of this study suggested that the heterozygote CT genotype of the ADRB3/rs4994 polymorphism is associated with a reduced risk of obesity among the Saudi population. In the future, larger scale studies are required to further confirm these observations.

Association of TNFA (-308G/A), IFNG (+874 A/T) and IL-10 (-819C/T) polymorphisms with protection and susceptibility to dengue in Brazilian population.

To evaluate gene polymorphisms and their association with susceptibility to dengue. A retrospective case-control study was performed with 262 subjects, comprising 78 dengue fever (DF) patients, 49 dengue hemorrhagic fever (DHF) patients and 135 healthy controls. Genotypic and allelic profiles were identified using polymerase chain reaction based in real time and amplification-refractory mutation system. We observed a protective association of IL-10 (-819C/T) C allele (P=0.028, OR=0.56, CI=0.34-0.91) against DHF, while the C/T (P=0.047, OR=2.10, CI=1.01-4.38) and T/T (P=0.008, OR=3.82, CI=1.38-10.59) genotypes were associated with DHF and DF, respectively. The dominant model TNFA -308GA+AA (P=0.043, OR=0.45, CI=0.20-1.00) genotypes were found to have protective effect against dengue infection. A protective association among the IFNG (+874 A/T) A/T genotype against DF (P=0.02, OR=0.46, CI=0.24-0.89) and DHF (P=0.034, OR=0.43, CI=0.19-0.95) was observed. When the studied single-nucleotide polymorphism was analyzed in combination, the combination GTA (P=0.022, OR=2.95, CI=1.18-7.41) was statistically significantly associated with susceptibility to DF and the combination GCT (P=0.035, OR=0.28, CI=0.08-0.90) with protection against the development of DHF. This research identifies the association of the IFNG (+874 A/T), TNFA (-308G/A), IL-10 (-819C/T) genotypes as a factor for protection, susceptibility and severity to dengue.

Malassezia Yeast and Cytokine Gene Polymorphism in Atopic Dermatitis.

Atopic Dermatitis (AD) is a recurrent chronic condition associated with microorganism and their interaction with the susceptible host. Malassezia yeast is a known commensal which is thought to provoke the recurrent episodes of symptoms in atopic dermatitis patients. Malassezia immunomodulatory properties along with defective skin barrier in such host, results in disease manifestation. Here, we studied Single Nucleotide Polymorphism (SNP) in IL10 and IFN γ genes of the host and its relation with susceptibility to Malassezia infection. To isolate Malassezia yeast from AD patients and compare the genetic susceptibility of the host by correlating the cytokine gene polymorphism with the control subjects. Study was conducted from January 2012 to January 2013. It was a prospective observational study done in Department of Microbiology and Department of Dermatology and Venereology in University College of Medical Sciences and GTB Hospital, Delhi. Sample size comprised of 38 cases each of AD. Skin scrapings were used for fungal culture on Sabouraud Dextrose Agar (SDA) and Modified Dixon Agar (MDA) and isolated were identified as per conventional phenotypic methods. Genomic DNA was extracted from blood samples collected from all study subjects. Cytokine genotyping was carried out by Amplification Refractory Mutations System- Polymerase Chain Reaction (ARMS-PCR) with sequence specific primers. Three SNPs (IL10-1082A/G; IL10-819/592C/T; IFN-γ+874A/T) in two cytokine genes were assessed in all the patients and healthy controls. Chi-Square Test or Fisher's-Exact Test and Bonferroni's correction. In AD group, Malassezia yeasts were cultured in 24 out of 38 samples and thus the identification rate was 63.1 percent as compared to healthy group, 52.6 percent (20/38). Significant difference in allele, or genotype distribution were observed in IL10-819/592C/T and IFN-γ+874A/T gene polymorphism in AD group. Higher isolation rate in cases as compared to control group highlights the implication of Malassezia in AD. Association between specific cytokine gene polymorphism and clinical outcome was found to be significant in study group. The result of cytokine gene polymorphism in the present study demonstrated susceptibility of host to Malassezia infection.

RFC1 80G>A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: a human genome epidemiologic review and meta-analysis of observational studies.

Associations have been reported between candidate genes and the response to methotrexate (MTX) in rheumatoid arthritis (RA) patients, but most of the studies have been small and have yielded conflicting results. This study was undertaken to provide a systematic review of all genetic variant associations with MTX efficacy and toxicity, and to conduct a meta-analysis evaluating the most commonly studied single-nucleotide polymorphism for which prior cumulative analysis has been lacking. A systematic review and meta-analysis were performed to identify genetic variant associations with MTX efficacy and toxicity. Studies were identified from the Medline, EMBase, HuGENet Navigator, and Cochrane Library databases through December 2012, and from the 2009-2011 abstracts of the American College of Rheumatology and the European League Against Rheumatism annual meeting proceedings. Additional unpublished genotype data from a Canadian cohort of patients with early RA were also included. Among the 87 identified studies examining genetic associations with MTX efficacy and toxicity, the reduced folate carrier 1 gene (RFC1) variant 80G>A (Arg(27) His, rs1051266) was selected for random-effects meta-analysis. RFC1 80G>A was associated with MTX efficacy in both the recessive model (odds ratio [OR] 1.42, 95% confidence interval [95% CI] 1.04-1.93) and the additive model (OR 1.28, 95% CI 1.10-1.49). Restriction of the sensitivity analyses to studies that involved Caucasian subjects only and that used similar outcome measures (MTX failure versus nonfailure) maintained and improved the associations in both models. No significant association between RFC1 80G>A and MTX toxicity was detected. In these analyses of available data from observational studies, RFC1 80G>A was found to be associated with MTX efficacy, but not toxicity, in RA patients. This variant merits further prospective analysis as a potential predictor of MTX efficacy. Variability in the definitions of response in pharmacogenetic studies is a source of data heterogeneity that should be addressed.

Cytotoxic T lymphocyte antigen-4 gene polymorphism in systemic lupus erythematosus Egyptian patients

The human cytotoxic T lymphocyte antigen-4 (CTLA-4) gene has been confirmed to be associated with several autoimmune diseases. In this study, we investigated the CTLA-4 gene polymorphism in systemic lupus erythematosus (SLE) Egyptian patients. A polymerase chain reaction was conducted to amplify CTLA-4 gene, followed by restriction fragment length polymorphism (RFLP) assay to detect candidate genetic polymorphism at positions -1722 T/C and -1661 A/G. Sixty SLE patients (55 females and 5 males) with mean age 28.5 ± 7 years and 40 healthy controls (31 females and 9 males) with mean age 27.8 ± 6.2 years were included in this study. The genotypic distribution at position -1661 of CTLA-4 gene was GG (11.7 %), AA (70 %), and AG (18.3 %) in SLE patients versus GG (20 %), AA (65 %), and AG (15 %) in the control (P value 0.508); regarding the position -1772 of CTLA-4 gene, the distribution was TT (83.3 %) and TC (16.7 %) in SLE patients versus TT (77.5 %) and TC (22.5 %) in the controls (P value 0.466). On studying the clinicopathological impact of the studied single nucleotide polymorphism (SNPs) with the disease severity, there is a statistical significance (P = 0.011) for the presence of AA genotype and severity of disease at -1661 genotype. AA genotype at -1661 was protective against discoid rash (P = 0.005), TC genotype at -1772 site is protective against serositis (P = 0.05), and serositis occurs more commonly with the AG genotype at -1661 site (P = 0.038). In our study, we concluded that the studied SNPs at positions -1772 and -1661 of CTLA-4 gene were not associated with SLE risk in Egyptian population.

P 79. Effects of brain derived neurotrophic factor polymorphism on cortical excitability measured by transcranial magnetic stimulation

Variation in the brain derived neurotrophic factor (BDNF) gene affects neural plasticity. With the commonly studied single nucleotide polymorphism (SNP) BDNF Val66Met, the Met allele is associated with reduced plasticity. However, little is known about the baseline excitability measures of rarer form Met/Met compared to other forms and the response to plasticity and metaplasticity protocols using transcranial magnetic stimulation (TMS). To investigate the effects of the BDNF Val66Met SNP on motor cortex excitability, inhibition, facilitation, plasticity and metaplasticity. From 177 healthy volunteers we selected 7 subjects with the rare (around 5–10% of population) Met/Met genotype and compared them to 9 age-and gender-matched Val allele carriers on various excitability measures using TMS. Motor threshold, recruitment curves, short and long interval intracortical inhibition (SICI and LICI), short interval intracortical facilitation (SICF) and time courses of these circuits were studied. Potentiation [high frequency rTMS and paired associative stimulation at 25 ms latency (PAS25)] and depression (low frequency rTMS and PAS10) protocols as well as interactions of these plasticity protocols (metaplasticity) were studied with sessions separated at least by a week (6 sessions in total). Met/Met subjects showed higher motor threshold (61.7 ± 8.6% stimulator output compared to 48.7 ± 9.5; p = 0.01), and less steep recruitment curves (significant main effects and interaction for BDNF genotype and TMS intensity). There was no significant difference between the groups in terms of intracortical inhibitory circuits, the time course and recruitment curves for SICI/LICI. There was a trend for reduced facilitation at the peaks (1.5, 3 and 4 ms) for SICF in Met/Met compared to non-Met/Met subjects. For plasticity protocols, there was significantly higher potentiation of MEP amplitude with high frequency rTMS (main effects of BDNF genotype) and a trend of greater MEP depression with PAS10 in non-Met/Met subjects. No difference was noted in the other plasticity and metaplasticity protocols. Met/Met subjects had higher motor threshold, less steep MEP recruitment curves and reduced peaks of SICF, implying lower cortical excitability compared to non-Met/Met genotypes. This decreased excitability in Met/Met subjects is associated with less potentiation induced by high frequency rTMS. Our study is ongoing and more subjects are being recruited to compare the three BDNF genotypes (Met/Met, Val/Met and Val/Val genotypes) of subjects. Support by Canadian Institutes of Health Research.

Genetic variation of apolipoproteins, diet and other environmental interactions; an updated review.

This paper summarizes the recent findings from studies investigating the potential environmental modulation of the genetic variation of apolipoprotein genes on metabolic traits. We reviewed nutrigenetic studies evaluating variations on apolipoproteins-related genes and its associated response to nutrients (mostly dietary fatty acids) or any other dietary or environmental component. Most revised research studied single nucleotide polymorphism (SNP) and specific nutrients through small intervention studies, and only few interactions have been replicated in large and independent populations (as in the case of -265T > C SNP in APOA2 gene). Although current knowledge shows that variations on apolipoprotein genes may contribute to the different response on metabolic traits due to dietary interventions, evidence is still scarce and results are inconsistent. Success in this area will require going beyond the limitations of current experimental designs and explore the hypotheses within large populations. Some of these limitations are being covered by the rapidly advance in high-throughput technologies and large scale-genome wide association studies.

Expression of pAkt affects p53 codon 72 polymorphism-based prediction of response to radiotherapy in nasopharyngeal carcinoma

BackgroundCodon 72 (Arg/Pro), the most frequently studied single nucleotide polymorphism (SNP) of p53 to date, is associated with the ability of the gene to induce cell apoptosis. The PI3K/Akt pathway plays an essential role in the transcriptional activation function of p53, and is an important factor in radiotherapy resistance. The present study was designed to evaluate the prediction of response to radiotherapy based on p53 codon 72 SNP and pAkt expression in biopsy specimens of locoregional nasopharyngeal carcinoma (NPC) before treatment.Materials and methodsIn total, 75 consecutive patients with locoregional NPC were enrolled. The p53 codon 72 SNP was identified from retrospectively collected paraffin-embedded biopsy specimens using Sanger sequencing. Expression patterns of p53, p21, 14-3-3σ, and pAkt proteins were investigated using immunohistochemical analyses. The effects of genetic polymorphisms and protein expression on progression-free survival (PFS) were evaluated using the Cox proportional hazards model, Kaplan–Meier method, and log-rank test.ResultsThe p53 codon 72 Pro/Pro carriers showed lower risk of disease progression (local recurrence and distant metastases) (HR: 0.300; 95% CI: 0.092–0.983; p=0.047). However, this association between the p53 codon 72 polymorphism and PFS was not significant in the pAkt-positive subgroup. No association was observed between protein expression of p53, p21 or 14-3-3σ and p53 codon72 polymorphisms. Notably, positive expression of p53 protein appeared to be correlated with poorer PFS among patients diagnosed as local regional lymph node metastasis (N+) before treatment (p=0.032).ConclusionsThe p53 codon 72 Pro/Pro genotype may be an effective independent prognostic marker for better outcome in patients with locoregional NPC. Based on the current findings, we hypothesize that pAkt weakens the predictive value of p53 codon 72 SNP in NPC. A combination of positive p53 protein expression and local regional lymph node metastasis may additionally be predictive of high risk of disease progression.

Genetic polymorphism study of the BCL-6 gene, in diffuse large B-cell lymphoma

Background: Diffuse large B-cell lymphoma (DLBCL) is characterized by a marked degree of morphologic and clinical heterogeneity. BCL-6 gene rearrangements are the most common frequent chromosomal abnormalities in DLBCL. Genetic modifications of the BCL-6 gene in lymphoma include translocations, deletions, and somatic mutations (SM) of the 5′-non-coding region. Mutations in the 5′-regulatory region of BCL-6 were suggested to play a role in non-Hodgkin's lymphoma (NHL) progression. Materials and Methods: We studied single nucleotide polymorphism (SNP) at position 397(G->C) of the 5'-non-coding regulatory region of BCL-6. We examined 30 patients with DLBCL treated at the National Cancer Institute (NCI), Cairo University, and 21 normal lymph nodes from patients with breast cancer were selected as controls. We used (Polymerase chain reaction- Restriction fragment length polymorphism) PCR-RFLP coupled analysis to detect the polymorphism. Results: From 30 patients with DLBCL, 17 were males (56.7%) and 13 were females (43.3%), the polymorphism G397C in the 5′ region of BCL-6 was detected in seven cases (23.3%). There was no significant association of clinical characteristics of DLBCL patients with this polymorphism, but there a trend for this polymorphism to occur more frequent in patients with aggressive disease. Conclusion: In our study, we found the incidence of the G397C SNP mutations in the 5′-regulatory region of BCL-6 to be 23.3%. No statistically significant association between the G397C SNP in BCL-6 gene with the standard clinico-pathological factors in patients with DLBCL was observed; however, there a trend for this polymorphism to occur more frequent in patients with aggressive disease.

Testing for genetic association between the ZDHHC8 gene locus and susceptibility to schizophrenia: An integrated analysis of multiple datasets

A number of studies have reported an association between the ZDHHC8 gene locus and schizophrenia but have produced some divergent findings and their interpretation is not straightforward. We investigated the association of the ZDHHC8 gene locus with schizophrenia using meta-analytic techniques, combining all published data up to May 2009 and focusing on 10 independent studies from six published references covering 2,894 cases, 2,932 controls and 1,225 parent-offspring trios. We restricted the analysis to studies investigating rs175174, the most frequently studied single nucleotide polymorphism (SNP). Stratified meta-analysis was conducted to investigate whether ancestry, study design, or gender moderated any association. Analyses of linkage disequilibrium (LD) and haplotype structure of this gene locus were also performed based on the hapmap project genotype data to determine whether there were other independent polymorphic markers which might contribute to susceptibility to schizophrenia in particular ethnic populations. We found no allelic- or genotype-wise evidence for an association of the rs175174 SNP with schizophrenia in our overall analysis. After applying stratified analyses, there was only a weak nominal genotype-wise association of this SNP with schizophrenia in the dominant genetic model in East Asian populations (P = 0.049), which might be caused by significant between-study heterogeneity (P = 0.042). No significant publication bias was detected. Other polymorphic markers within this gene genotyped in the hapmap project across different ethnic populations were in strong LD with rs175174. Consistently negative associations were found in the rs175174 polymorphism. LD structure further suggested that the ZDHHC8 locus might not play an important role in the etiology of schizophrenia.

R72P Polymorphism of TP53 in Ulcerative Colitis Patients is Associated with the Incidence of Colectomy, Use of Steroids and the Presence of a Positive Family History

P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR = 3.03; 95%CI = 1.91-2.40; p = 0.003), but only modest association with UC (OR = 1.61; 95%CI = 0.98-2.65; p = 0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR = 8.0; 95%CI = 1.68-38.08, p = 0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR = 17.77; 95%CI = 0.98-323.34, p = 0.012) and steroid use (OR = 10.14; 95%CI = 2.63-39.12, p = 0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.

A protocol comparison for the analysis of heat shock protein A1B +A1538G SNP

Heat shock proteins act as molecular chaperones, assist in peptide maturation, and transport nascent peptides across membranes. One commonly studied single nucleotide polymorphism (SNP) for one of the proteins is HSPA1B (+A1538G). However, several studies of this polymorphism have failed to achieve Hardy-Weinberg equilibrium (HWE) for their sample. We compared various published procedures for analyzing the HSPA1B +A1538G SNP and report reasons for HWE discrepancies. Samples from 141 apparently healthy, physically active, volunteers (99 men and 42 women) were analyzed. The first protocol, initially described by Schröder et al., resulted in a genotypic distribution of 22 GG (15.6%), 119 AG (84.4%), and 0 AA; results were confirmed by reanalysis and sequencing. Two other published protocols, one described by Klausz et al. and another by Fekete et al., were used to confirm these results: both resulted in 22 GG (15.6%), 46 AA (32.6%), and 73 AG (51.7%). Additionally, the results were within HWE and confirmed by sequence analysis. Of the original 119 subjects genotyped as AG by the Schröder protocol, 46 of those were confirmed as AA with the Klausz and Fekete methods. Mixing primers from the Schröder and Klausz protocol resulted in 100% concordance with the data generated by the Klausz and Fekete protocols. Some published data on HSP genotyping deviate from HWE; thus, primers used for analyzing these highly homologous genes must be carefully considered. Our results highlight the importance of reinvestigating data when HWE is not achieved for the HSPA1B, or another, polymorphism.