Hardy-Weinberg Equilibrium In Cases Research Articles

Potential genetic polymorphism of matrix metalloproteinase (MMP)-9 in Iranian migraine patients with Toxoplasma gondii infection.

Toxoplasma gondii is an intracellular protozoan parasite that causes neuroinflammation in the brain and a constant need for peripheral leukocyte migration. Matrix metalloproteinase 9 (MMP-9) can play a major role in this neuroinflammation and be implicated in some neurological disorders, such as migraines. Therefore, the genetic polymorphism evaluation of MMP-9 in migraine patients with T. gondii infection was performed. One hundred fourteen migraine patients and 114 healthy controls were evaluated for the presence of anti-Toxoplasma IgG antibodies. Seventy-two migraine patients and 40 healthy controls were randomly selected for assessment of the MMP 9-1562C/T genetic polymorphism. In the preliminary examination, 61 (53.5%) migraine patients and 43 (37.3%) healthy controls were positive for IgG antibodies, with a significant association between T. gondii seropositivity and migraine (OR = 1.90; 95% CI = 1.21-3.223; P = 0.012). Genetic distribution for the polymorphism was not in Hardy-Weinberg equilibrium in cases but showed no significant variation in control groups (P = 0.03 and P = 0.180, respectively). A significant preponderance of the CT + TT genotype was found in migraine subjects compared to controls (P = 0.042) (OR, 1.77, CI, 1.013-2.229). The homozygote muted allele TT had a higher rate in migraine patients (6.9%). There were significant differences in CT + TT genotype between T. gondii positive and negative migraine patients (P = 0.024), but T allele frequencies had no significant variation (OR 1.7 CI, 1.084-2.44 and 0.42 CI, 0.044-3.97, respectively). In conclusion, the results may provide the first evidence for the involvement of the MMP-9 gene polymorphism in the mechanism of migraine pathology following Toxoplasma infection.

Association study of Interleukin 10 gene polymorphisms in Iraqi patients with multiple sclerosis

Multiple sclerosis (MS) is a type of autoimmune disease where immune cell attacks our cells mistakenly; its severity is measured by expanded disease status scale (EDSS). The study aims the investigation of −1082 polymorphism in interleukin 10 (IL-10) as one of the etiologies that develops the disease. This is a case-control study that allele-specific polymerase chain reaction (AS-PCR) were provided to compare 100 relapsing-remitting MS (RRMS) patients, which fulfills McDonald criteria with 100 healthy controls depending on the −1082 (G/A) polymorphism of the gene encoding IL-10. The A allele frequency of IL-10 gene has been considerably less in MS patients compare to healthy control (60.50 Vs. 81%). Genotype distributions of the single nucleotide polymorphism (SNP) -1082 fulfills Hardy-Weinberg equilibrium in cases (P = 0.155) but it doesn't in controls (P < 0.0001). In MS patients, Heterozygous (GA) genotypes were non-significantly associated with MS (OR = 0.834,95% CI = 0.6890 to 1.29, P 0.706) but homozygous (AA) were significantly associated with this condition (OR = 3.420, 95% CI = 1.450 to 8.065, P = 0.0037). To conclude, the genotype distribution of −1082 (G/A) polymorphism has been showed a significant difference in the case/control study recruited in Erbil province-Iraq, and EDSS is significantly higher in A allele's carrier genotypes. There was non-significance association AA genotypes and duration of the disease.

Assessment of association between the rs2270637 polymorphism of VMAT1 gene and risk of bipolar and major depressive disorders

BackgroundVesicular monoamine transporters (VMATs) are important transporters which are expressed in the brain tissue and participate in the pathogenesis of neuropsychiatric disorders. VMAT1 gene has a missense single nucleotide polymorphism (SNP) (rs2270637 [Thr98Ser]) whose association with neuropsychiatric conditions has been assessed in different populations. MethodsIn the current study, we genotyped the rs2270637 SNP in 137 patients with bipolar disorder 1 (BPD1), 99 patients with BPD2, 55 patients with major depressive disorder (MDD) as well as sex and age-matched controls. Genotyping was performed using tetra-primer amplification-refractory mutation system -PCR and agarose gel electrophoresis. ResultsThe frequencies of genotypes of this SNP were in accordance with the Hardy-Weinberg equilibrium in cases and controls. There was no significant difference in frequencies of G and C alleles between BPD1 cases and controls (OR (95% CI) = 1.00 (0.65–1.52), P value = .99), between BPD2 cases and controls (OR (95% CI) = 1.08 (0.65–1.82), P value = .76), or between MDD cases and controls ((OR (95% CI) = 1.53 (0.81–2.88), P value = .18). No significant association was detected between the rs2270637 and any of BPD1, BPD2 and MDD conditions in allelic, recessive, dominant or co-dominant models. ConclusionThus, the rs2270637 SNP cannot be regarded as a risk locus for BPD or MDD in Iranian population.

Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians.

Inflammatory bowel disease (IBD) is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs) in the autophagy related 16 like 1 (ATG16L1) gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn’s disease (CD), 249 patients with ulcerative colitis (UC) and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD) values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D’ = 0.76–1.0) and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10−6 for CD and 0.002 for UC). SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.

Polymorphisms In Thrombin-Activatable Fibrinolysis Inhibitor and Plasminogen Activator Inhibitor Type 1 In Women With Primary Recurrent Pregnancy Loss

Introduction Recurrent pregnancy loss (RPL) is defined as three or more consecutive spontaneous abortions prior to the 20th week. RPL is a multifactorial condition that could be influenced by several factors, including haemostasis disorders. Indeed, pregnancy is characterized by a hypercoagulable state in which levels of some coagulation factors and fibrinolytic inhibitors are increased, whereas levels of the natural anticoagulant free protein S are decreased. Therefore, an unbalance in the fibrinolytic system might be involved in the pathophysiology of RPL. Plasminogen activator inhibitor type 1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) are two fundamental inhibitors of fibrinolysis, whose levels could be influenced by genetic polymorphisms. Aims: To investigate the frequencies of polymorphisms in PAI-1 (SERPINE1 4G/5G) and TAFI (CPB2 c.505G&gt;A) in women with primary RPL and in healthy women. Materials and Methods We included 116 unrelated non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability (primary RPL) who were evaluated in the Prenatal Care Unit at the Hospital of the University of Sao Paulo. The control group was comprised of 263 unrelated healthy fertile women who were users of Public Health Service or employees of the University of Sao Paulo, who had at least two term deliveries and no known pregnancy losses as well as known medical history of thrombosis, diabetes, hypertension, cancer and autoimmune disorders. Both cases and controls were from the general urban population of Sao Paulo City. The genotypes for CPB2 c.505G&gt;A polymorphism were performed by Real Time PCR, and genotypes for SERPINE1 4G/5G polymorphism were performed by RFLP-PCR. The effect of these polymorphisms on RPL risk was assessed by calculating Odds ratios (OR) and their 95% confidence intervals (CI) by logistic regression. Results and Conclusions The genotype distribution of both polymorphisms was in Hardy-Weinberg equilibrium in cases and in controls (p&gt;0.05). The genotype and allele frequencies for SERPINE1 4G/5G and CPB2 c.505G&gt;A polymorphisms were similar in both groups (p&gt;0.05). For SERPINE1 4G/5G polymorphism, 70 cases (60.4%) and 152 controls (57.8%) were carriers of the 4G allele, yielding an OR of RPL of 1.11 (95% CI: 0.71 - 1.74, p= 0.642) (genotype 5G5G vs. 4G5G + 4G4G). For CPB2 c.505G&gt;A polymorphism, 64 cases (55.2%) and 153 controls (58.2%) were carriers of the A allele, yielding an OR of RPL of 0.88 (95% CI: 0.57 - 1.37, p= 0.586) (genotype GG vs. GA + AA). Furthermore, similar frequencies of minor allele were found in groups when the number of losses was considered in RPL group (women with four or more RPL vs. women with three, p &gt;0.05) and when the period of pregnancy loss was considered (women with early losses vs. women with late losses, p&gt;0.05). Our data suggest that polymorphisms in SERPINE1 and CPB2 are not associated with a risk of having RPL. Financing: FAPESP (Proc 2007/57605-0), CAPES. Disclosures: No relevant conflicts of interest to declare.

Association of 14‐bp insertion/deletion polymorphism of HLA‐G gene with unexplained recurrent spontaneous abortion: a meta‐analysis

A meta-analysis was performed to assess the association of the human leukocyte antigen-G (HLA-G) 14 bp insertion (ins)/deletion (del) polymorphism with unexplained recurrent spontaneous abortions (URSA). The fixed or random effect pooled measure was selected based on the homogeneity test among studies that was evaluated with I². Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. In this meta-analysis, 14 studies with 1464 cases and 1247 controls corresponded to the inclusion criteria were included. Significant associations between 14 bp ins/del polymorphism and risk of URSA were observed in both dominant [random effect model (REM) OR = 1.469, 95% CI = 1.127-1.914] and codominant (REM OR = 1.195, 95% CI = 1.005-1.420) models. After excluding two articles that deviated from Hardy-Weinberg equilibrium in cases and sensitivity analysis, significant associations were also observed in dominant [fixed effect model (FEM) OR = 1.224, 95% CI = 1.020-1.470] and codominant (FEM OR = 1.158, 95% CI = 1.028-1.305) models. This meta-analysis suggests that the 14 bp ins HLA-G allele is associated with increased risk of URSA. The results are of importance to the clinical practice of URSA and infertility.

NAD(P)H:Quinone Oxidoreductase 1 (NQO1) P187S Polymorphism and Prostate Cancer Risk in Caucasians

NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen. A “C” to “T” transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity. No NQO1 protein activity was detected in NQO1 609TT genotype, and low to intermediate activity was detected in NQO1 609CT genotype compared with 609CC genotype. Thus, this polymorphism may result in altered cancer predisposition. For prostate cancer, only sparse data are available. We therefore analyzed the distribution of the NQO1 P187S SNP (single nucleotide polymorphism) in prostate cancer patients and a healthy control group. Allelic variants were determined using RFLP analysis. Overall, 232 patients without any malignancy and 119 consecutive prostate cancer patients were investigated. The genotype distribution in our cohorts followed the Hardy–Weinberg equilibrium in cases and controls. The distribution of the NQO1 codon 187 SNP did not differ significantly between prostate cancer patients and the control group (p = 0.242). There was also no association between the allelic variants and stage or Gleason score of the tumors. The NQO1 P187S SNP was not significantly associated with an increased prostate cancer risk in our cohorts. The SNP has also no influence on histopathological characteristics of the tumors. A combined analysis of all available data from published European studies also showed no significant differences in the genotype distribution between controls and prostate cancer patients. Our data suggest a minor role of the NQO1 nucleotide 609 polymorphism in prostate carcinogenesis.

14-OR

Aim The HLA class II gene BCL2-associated athanogene 6 (BAG6, previously BAT3) is induced by heat shock. Its product is a ligand for NKp30 receptor of NK cells, and is also involved in apoptotic pathways through interactions with caspase and P53. Its SNP rs3117582 is associated with lung cancer risk. Our previous work showed that it is exclusively present on the conserved extended haplotype (CEH) 8.1 (B8DR3). We aimed to clarify whether this SNP is the primary association or a proxy for a CEH8.1 association by bioinformatics and experimental approaches. Methods We examined the rs3117582 association in a case-control study using BioServe Lung Cancer SNPlates (180 cases and 180 controls). For bioinformatics analysis, we used tools available online. For functional replication, we assessed the correlation of this SNP with BAG6 expression using TaqMan analysis on 15 HLA homozygous IHWG cell lines. We used HSPA1B expression to control the experimental approach and for comparison. Results Bioinformatic analysis predicts alteration of heat shock factor binding site by this SNP (FS score = 0.242). The case-control study replicated the previously reported association with lung cancer risk (OR (recessive model) = 5.2, 95% CI = 1.1 to 23.5, P = 0.02) compounded by violation of Hardy-Weinberg equilibrium in cases ( P = 0.001), but not in controls ( P = 0.63). The cell line COX carrying CEH8.1 was homozygous for BAG6 rs3117582 allele C. It showed the expected heat shock response in HSPA1B expression comparable to all other cell lines. The BAG3 expression was increased up to four-fold with heat shock, but COX did not respond that well and ranked 10 among 15 cell lines. Conclusions We replicated the BAG6 rs3117582 association in lung cancer, and also performed functional replication by experimentally confirming bioinformatically predicted function. Given the evidence that this SNP is also involved in breast cancer susceptibility, BAG3 may be a general cancer susceptibility gene located in the central HLA complex.

A Polymorphism of the ORAI1 Gene is Associated With the Risk and Recurrence of Calcium Nephrolithiasis

Store-operated calcium entry has been considered an important factor to regulate inflammatory reactions in nonexcitable cells. However, the effects of genetic polymorphisms of ORAI1, a main component of store-operated calcium channels, on nephrolithiasis and stone recurrence remain unclear. We investigated the association between calcium containing nephrolithiasis and genetic variants of ORAI1 gene in Taiwanese patients. A case-control study was performed in 136 patients with nephrolithiasis and 500 controls. Five tagging single nucleotide polymorphisms of ORAI1 were selected for genotyping. ORAI1 genotypes were determined by TaqMan® assay. Hardy-Weinberg equilibrium in cases and controls was assessed, and genetic effects were evaluated by the chi-square test and sliding window haplotype analysis. Subset analysis was done according to family history. Two single nucleotide polymorphisms (rs12313273 and rs6486795) of the ORAI1 gene were associated with the risk of nephrolithiasis. The C allele carrier for rs12313273 was strongly related to recurrent stone forming in patients. On sliding window analysis the results of the 2 (rs12313273 and rs7135617) and the 3 (rs12313273, rs7135617 and rs6486795) single nucleotide polymorphism haplotypes had more significant effects on the risk of nephrolithiasis than the single nucleotide polymorphism rs12313273. To our knowledge this is the first study identifying the novel polymorphisms of the ORAI1 gene, which may predispose to the risk of calcium nephrolithiasis and disease recurrence.

Inspection of a deviation from Hardy–Weinberg equilibrium in familial breast cancer cases from a case–control study in a meta-analysis

We have read with interest the article by Ziegler et al. [1] in which the authors have developed a meta-analytic framework for assessing compatibility with Hardy–Weinberg equilibrium (HWE) or measuring deviation from HWE (HWD). The authors argue that the standard HWE v lack of fit test is logically flawed; subsequently, they provide a logically unflawed approach for measuring HWD using confidence intervals. It is a professionally written article with a state-of-the-art statistical method to advocate the use of a confidence interval-based approach to assess HWE. Similarly, the authors try to refute our critique of a study by Frank et al. [2], of which we had expressed our opinions in a letter published in Breast Cancer Res Treat [3] as follows: (1) we pointed out that Frank et al. had reported an incorrect result of HWE (they declared that no HWD was observed in cases and controls, but an HWD was in fact excised in a case group with a P value of 0.048, i.e., a significance level of 0.05), and (2) we encouraged the authors to ‘‘discuss the potential influence of HWD on the results of that study.’’ Aiming to refute our statement, Ziegler et al. [1] argued the following: (1) HWD in cases could indicate a genetic association; testing for HWD in cases is not meaningful for quality control therefore not necessary. (2) Using a confidence interval method, they were able to show that control groups and overall samples were in sufficiently good agreement with HWE. We reply to Ziegler et al. with the following arguments: First, our critique was NOT that Frank et al. ought to test HWE in cases, BUT that if Frank et al. chose to test HWE in cases (they actually did. See RESULTS of Ref. [2] p. 142, column 1, row 23), they should have reported the true data (they actually did not. As mentioned above, an HWD was observed in cases but Frank et al. reported none). We also encouraged them to carry out a discussion for an HWD in cases if it was necessary (they actually did not). Second, now that Frank et al. tested HWE in cases and an HWD was actually observed, what should be done subsequently? Ziegler et al. insisted that an HWD in cases may reflect a genetic association, and checking genotyping errors (which is costly) would not make much sense. They even rejected further scrutiny of the reason and effect of HWD in cases in Frank’s study, but preferred to analyze possible heterogeneity in HWD between controls from substudies in that meta-analysis. Unlike the former, we did not take for granted that every HWD in cases indicates a probable genetic association; similarly, we did not think that discussing HWD in cases in Frank’s study is just a waste of time. Consequently, let us sketch the possible reasons behind the HWD and discuss them individually. K.-D. Yu Z.-M. Shao (&) Department of Breast Surgery, Cancer Institute and Cancer Center, Fudan University, 399 Ling-Ling Road, Shanghai 200032, People’s Republic of China e-mail: zhimingshao@yahoo.com

A 5′ promoter region SNP in NRG1 is associated with schizophrenia risk and type III isoform expression

A 5′ promoter region SNP in NRG1 is associated with schizophrenia risk and type III isoform expression

CHOP5'UTR-c.279T&gt;C and +nt30C&gt;T variants are not associated with overweight condition or with tumors/cancer in Italians – a case-control study

BackgroundType 2 diabetes (T2D) is associated with obesity and has been shown recently to be associated with tumors/cancer. HNF1-beta and JAZF1 genes are associated with T2D and prostate cancer. We have previously shown that CHOP 5'UTR-c.279T>C and +nt30C>T haplotype variants contribute to T2D. CHOP deficiency causes obesity in mice, thus CHOP gene variants may contribute to human obesity. Furthermore, CHOP mediates apoptosis and is implicated in cancer pathogenesis. Hence, we aimed at identifying any potential association of CHOP 5'UTR-c.279T>C and +nt30C>T genotypes and corresponding haplotypes with overweight condition/pre-obesity and tumors/cancer in an Italian dataset.MethodsWe recruited from Italy 45 overweight subjects (body mass index (BMI) ≥ 25) and 44 control subjects (BMI < 25) as well as 54 cases with at least one cancer or at least one tumor and 43 control subjects without tumors/cancer from the general population. We excluded allelic departure from Hardy-Weinberg equilibrium in cases and control subjects, separately.ResultsWe assessed the power to detect risk odds ratios by association tests in our datasets. We tested the hypothesis of association of CHOP 5'UTR-c.279T>C and +nt30C>T genotypes and haplotypes with tumors/cancer and, separately, with overweight condition. Both associations were not significant.ConclusionFrom our study, we may conclude that CHOP 5'UTR-c.279T>C and +nt30C>T genotypes and corresponding haplotypes are not associated with tumors/cancer and pre-obesity. However, more studies are warranted to establish the role of CHOP variants in tumor/cancer predisposition and in overweight condition.

APRIL polymorphism and systemic lupus erythematosus (SLE) susceptibility

Two novel non-synonymous polymorphisms of the APRIL gene, codon 67 (rs11552708) and 96 (rs3803800), were recently identified and tested for disease association. The 67G allele was reported to be associated with systemic lupus erythematosus (SLE) in a Japanese population. The aim of the study is to investigate whether the APRIL polymorphism associated with susceptibility to SLE in a Japanese population is associated with the susceptibility to SLE in other ethnic groups. Three hundred and forty-eight SLE patients (204 European-American, 103 African-American and 41 Hispanic) and 345 ethnicity-matched controls (201 European-American, 104 African-American and 40 Hispanic) were included from the Lupus Multiplex Registry and Repository (LMRR) and evaluated for genetic association. The APRIL codon 67 and codon 96 were genotyped by a 3-base extension method. Statistical evaluations were performed using both chi-square and logistic regression analysis. Both the single-nucleotide polymorphisms (SNPs) were in Hardy-Weinberg equilibrium in cases and controls within each ethnic group. The APRIL codon 67 was significantly associated with SLE risk under the dominant model adjusted by ethnicity (odds ratio, 95% confidence interval and P-values were 1.45 and 1.02-2.06 and 0.036, respectively). Race-specific analysis also showed a trend for association in African-American and Hispanic SLE subjects. CONCLUSION The APRIL codon G67R polymorphism associated with SLE in a Japanese population may also be associated with SLE in other populations.

Vitamin D Receptor Polymorphism among Rickets Children in Mongolia

BACKGROUNDIt was reported that 32% of children under five years old in Mongolia had symptoms of rickets. Vitamin D receptor (VDR) gene polymorphism has received attention in relation to bone metabolism. We therefore investigated whether VDR polymorphism is related to high prevalence of rickets in Mongolia and to bone properties in childhood.METHODSWe conducted a case-control study in Ulaanbaatar involving 80 children aged 7-10 years with a history of rickets (cases) and 72 children with no history of rickets (controls). VDR polymorphism was assessed using BsmI, ApaI, and TaqI, and bone properties were determined by measuring age-standardized midtibial cortical speed of sound (TCSOS).FINDINGSEach allelic frequency was verified to satisfy the Hardy-Weinberg equilibrium in cases, controls, and the total sample. The VDR polymorphisms among cases (BB 3%, Bb 18%, bb 80%; AA 15%, Aa 38%, aa 47%; and TT 81 %, Tt 17%, tt 3%) did not differ significantly from those among controls (BB 1%, Bb 13%, bb 86%; AA 16%, Aa 46%, aa 38%; and TT 86%, Tt 13%, tt 1%). There were no significant differences in TCSOS according to the VDR genotype among either cases or controls.CONCLUSIONSThe VDR polymorphism does not play a major role in the development of rickets in Mongolia and has no effect on TCSOS in childhood.

No association between genetic polymorphisms of the Interleukin-4 Receptor alpha gene and cervical cancer in Korean population

Objective: Genetic variants of polymorphisms of Ile50Val were known to upregulate receptor response to IL-4. IL-4 was found in cervical cancer cell lines and known to promote cervical carcinogenesis and the progression from cervical intraepithelial neoplasia to cervical cancer. So, we aim to explore whether the Ile50Val polymorphisms of Interleukin-4 receptor alpha () gene increase cervical cancer risk, which could serve as useful genetic markers for assessing the risk of the development and progression of cervical cancer in Korean population. Methods: The blood samples of 228 cervical cancer patients who were diagnosed at Seoul National University Hospital from 1999 to 2002 and 204 subjects who had screened at the health care system of Seoul National University Hospital and confirmed as non-cancer controls, were obtained. PCR amplification and TagMan assay were used. We used the chi-square test to evaluate whether the distribution of genotypes varied significantly between cervical cancer and controls. Odds Ratio and 95% confidence intervals were calculated using logistic regression test after age adjusting. Results: The distribution of homozygotes and heterozygotes closely approximated the expected values under Hardy-Weinberg equilibrium in cases and controls (p=0.33, chi-square=0.94; p=0.15, chi-square=2.04). In cervical cancer group, allele frequency of Ile was 46.1%, in comparison with 43.4% in control group which showed no significant difference statistically (p=0.52). Using subject with the Val/Val homozygote as a reference group, we found no association between the Ile/Val and Ile/Ile genotypes and the risk of cervical cancer with age adjusted regression analysis (=1.09, 95% CI=0.70-1.72, p=0.7; =1.21, 95% CI=0.67-2.19, p=0.52). Subanalyses of the cervical cancer according with clinical stage, histologic type, lymph node status and parametrial invasion status showed no statistically significant association with these polymorphisms. Conclusion: The polymorphisms of the gene are neither associated with increasing risk of cervical cancer nor more vulnerable for cervical cancer progression in Korean population.

Polymorphisms in Interleukin -2, -6, and -10 Are Not Associated with Gastric Cardia or Esophageal Cancer in a High-Risk Chinese Population

Polymorphisms in Interleukin -2, -6, and -10 Are Not Associated with Gastric Cardia or Esophageal Cancer in a High-Risk Chinese Population

Polymorphisms of the NADPH Oxidase p22phox Gene in a Caucasian Population with Intracranial Aneurysms

Background: Vascular remodeling generated by reactive oxygen species contributes to aneurysm formation. The NADPH oxidase system is a major source of superoxide anion not only in phagocytes, but also in endothelial and vascular smooth muscle cells. Polymorphisms of p22phox, an essential component of the NADPH oxidase system, are found to be associated with atherosclerosis, while a recent study found a significant association between the 214C>T polymorphism and the occurrence of ischemic cerebrovascular disease. We conducted a case-control study to investigate the relationship of five polymorphisms of the p22phox gene and the occurrence of cerebral aneurysms. Methods: The study population consisted of 113 patients with intracranial aneurysms and 53 control subjects. The 214C>T polymorphism was investigated by restriction fragment length polymorphism analysis, while polymorphisms 381T>C, 480G>A, 521C>T, and *24A>G were analyzed by direct sequencing of exon 6 and adjacent intronic sequences. Results: The analysis of a primary study sample comprising 35 cases and 28 controls failed to show a significant association between any of the five polymorphisms and the occurrence of intracranial aneurysms using both allele frequencies and genotypes (all nominal p > 0.05). Although there was a deviation from Hardy-Weinberg equilibrium in cases at the 521C>T locus (nominal p < 0.05), this could not be confirmed in a second study sample of 78 patients. Haplotypes were constructed regarding three frequent polymorphisms (214C>T, 521C>T, and *24A>G); haplotype frequencies in cases and controls were not significantly different. Conclusion: Although polymorphisms of the p22phox gene located in the coding region and the 3′-untranslated region were reported to be associated with atherosclerosis and cerebrovascular disease, our data provide evidence that there is no association between these polymorphisms and the occurrence of cerebral aneurysms in Caucasians.