Genetic variation in DNA repair genes can modulate DNA repair capacity and may be related to the risk of cancer. The human papillomavirus is considered to be a necessary but not sufficient cause for ...cervical cancer and, therefore, other factors contribute to the carcinogenesis. A hereditary component for this neoplasia has been reported. Evaluation of the association of six polymorphisms was carried out in the following DNA repair genes: XRCC1 (Arg194Trp, Arg280His, and Arg399Gln), ERCC1 (Asp118Asp), ERCC2 (Lys751Gln), and ERCC4 (Arg415Gln). The cases (n = 110) included 65 squamous cell carcinomas (SCCs) and 45 squamous intraepithelial lesions (SIL). Controls (n = 68) were recruited from among women without cervical abnormalities. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. A positive association was observed between the polymorphisms of XRCC1 genes, that is, in codons 194 P = 0.001, odds ratio (OR) = 20.1, 95% confidence interval (CI) = 5.9–68.8, 280 (P = 0.001, OR = 5.4, 95% CI = 2.3–12.6), and 399 (P = 0.008, OR = 4.2, 95% CI = 1.5–12.1) and cervical cancer. SIL patients also showed a significant association with codon 194 (P = 0.012, OR = 3.8, 95% CI = 1.3–10.6), but not with 280 (P = 0.35) and 399 (P = 0.81). A positive correlation was also found in ERCC4 Gln415Gln in both SCCs and SILs (P = 0.001, OR = 21.3, 95% CI = 7.1–64.0 and P = 0.001, OR = 7.8, 95% CI = 2.9–20.9, respectively). For ERCC2 Gln751Gln, the association was significant for both SCCs (P = 0.001, OR = 10.1, 95% CI = 2.6–37.9) and SILs (P = 0.001, OR = 8.9, 95% CI = 2.8–28.3). However, the risk of SCC did not appear to differ significantly among individuals with the ERCC1 Asp118Asp genotype (P = 0.404). For SILs, it appeared to be a protective genotype (95% CI = 0.1–0.7). This study indicates that variant types of DNA repair genes play an important role in modifying individual susceptibility to SCC.
The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, ...including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans.
We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and ≈2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (λ range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (λ: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0 × 10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0 × 10(-8)).
This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent.
To investigate the genetic data of 21 autosomal STR included in Goldeneye™ DNA ID 22NC Kit in Chinese Han nationality and to evaluate the forensic application.
By detected 500 unrelated healthy ...individuals in Chinese Han nationality of East China with Goldeneye™ DNA ID 22NC Kit, allele frequencies, population genetics parameters and linkage disequilibrium information of the 21 autosomal STR were statistically analyzed.
In the 21 autosomal STR, no deviations from Hardy-Weinberg equilibrium were detected and all loci were independent form each other. DP values of 21 autosomal STR were all above 0.85, and the combined discrimination power was 1-3.616 5 x 10(-26). Combined mean exclusion chance of this system in duo cases was 1-2.786 81 x10(-6), in trio cases was 1-8.545 82 x 10(-1).
Twenty-one autosomal STR included in Goldeneye™ DNA ID 22NC Kit are highly polymorphic in the Han nationality. Combined with Goldeneye™ DNA ID 20A Kit, the kit can satisfy the needs for full-sibling testing and facilitate the solutio
Ovarian cancer is the second most common gynecologic cancer among women and the second leading cause of death from gynecologic malignancy worldwide. Androgens, acting through androgen receptors ...(ARs), have been implicated in the disease, while progestins, acting through progesterone receptors (PGRs), may provide protection against the disease. The PGR gene contains several polymorphisms in the hormone-binding domain, three of which are in linkage disequilibrium (a complex referred to as PROGINS). PROGINS has been associated with increased risk of ovarian cancer. This association has not been found consistently, and it may be limited to women who do not use oral contraceptives. The AR gene contains a trinucleotide CAG repeat, the length of which has been inversely associated with the ability of the AR-ligand complex to transactivate androgen-responsive genes. Data on the association between the AR repeat length and ovarian cancer, both in general and among carriers of mutations in the breast cancer 1 and 2 (BRCA1/2) genes, are inconclusive. There is insufficient evidence that polymorphisms in either the PGR gene or the AR gene may be a risk factor for ovarian cancer, alone or in combination with other factors. The sensitivity, specificity, positive and negative predictive values, and clinical validity of the PROGINS and AR CAG repeat assays are unknown. No recommendations for population-based screening can be made.
Degradation of extracellular matrix support in the large abdominal arteries contribute to abnormal dilation of aorta, leading to abdominal aortic aneurysms, and matrix metalloproteinase-9 (MMP-9) is ...the predominant enzyme targeting elastin and collagen present in the walls of the abdominal aorta. Previous studies have suggested a potential association between MMP-9 genotype and abdominal aortic aneurysm, but these studies have been limited only to the p-1562 and (CA) dinucleotide repeat microsatellite polymorphisms in the promoter region of the MMP-9 gene. We determined the functional alterations caused by 15 MMP-9 single-nucleotide polymorphisms (SNPs) reported to be relatively abundant in the human genome through Western blots, gelatinase, and promoter-reporter assays and incorporated this information to perform a logistic-regression analysis of MMP-9 SNPs in 336 human abdominal aortic aneurysm cases and controls.
Significant functional alterations were observed for 6 exon SNPs and 4 promoter SNPs. Genotype analysis of frequency-matched (age, sex, history of hypertension, hypercholesterolemia, and smoking) cases and controls revealed significant genetic heterogeneity exceeding 20% observed for 6 SNPs in our population of mostly white subjects from Northern Wisconsin. A step-wise logistic-regression analysis with 6 functional SNPs, where weakly contributing confounds were eliminated using Akaike information criteria, gave a final 2 SNP (D165N and p-2502) model with an overall odds ratio of 2.45 (95% confidence interval, 1.06-5.70).
The combined approach of direct experimental confirmation of the functional alterations of MMP-9 SNPs and logistic-regression analysis revealed significant association between MMP-9 genotype and abdominal aortic aneurysm.
In recent years, studies focussing on a possible association between the dopamine D4 receptor (DRD4) gene exon III polymorphism and the personality trait of novelty seeking (NS) have yielded ...inconsistent results. The present study sought to examine the association of the DRD4-7r allele with NS in a sample of 303 15-year-old adolescents (144 males, 159 females) using data from a high-risk community sample. The Junior Temperament and Character Inventory--JTCI/12-18 was administered to assess dimensions of adolescent temperament. Males in the DRD4-7r allele group scored significantly higher on the NS (p=.002) and the harm avoidance (p=.045) scales than males without this allele. In females no association with temperament was observed. This association could not be explained by the presence of either an attention-deficit/hyperactivity disorder (ADHD) or a DRD4 by ADHD interaction.
Aims The adrenergic nervous system is of major importance in congestive heart failure. No genetic polymorphism has previously been identified in the beta1-adrenergic receptor gene. The aim of this ...study was to find possible mutations in this gene and to relate such findings to morbidity and prognosis in heart failure. Methods and Results Genomic DNA was extracted from blood leukocytes from patients with congestive heart failure (n=184) and from age-matched controls (n=77). The part of the beta1-adrenergic receptor gene corresponding to nucleotide 1–255 was amplified by polymerase chain reaction and analysed by automated sequencing. The patients were investigated by echocardiography and followed regarding symptoms and survival for 5 years. A missense mutation was identified at nucleotide position 145 in the beta1-adrenergic receptor gene, which predicted an amino acid substitution at position 49 (Ser49Gly). The allele frequency of the Gly49 variant was 0·13 in controls and 0·18 in patients (P=0·19). At the time of the 5-years follow-up, 62% of the patients with the wild type gene and 39% of the patients with the Ser49Gly variant had died or had experienced hospitalization (P=0·005). Patients without the mutation had significantly poorer survival compared to those with the mutation, risk ratio 2·34 (95% CI 1·30–4·20), P=0·003. In a mulivariate analysis, the risk ratio was 2·03 (95% CI 0·99–4·16)P =0·05. Conclusion A novel missense mution in the beta1-adrenergic receptor gene was associated with a decreased mortality risk in patients with congestive heart failure. These data suggest that the beta1-receptor Ser49Gly variant might be associated with altered receptor function, resulting in myocardial protection in patients with heart failure.
Recurrent pregnancy loss (RPL) is caused by different factors, including genetics and thrombophilia. Beside Factor V Leiden, another nucleotide change in a factor V (FV) gene (A4070G; His1299Arg) has ...been identified linking to hereditary thrombophilia. Also, two proposed MTHFR polymorphisms, C677T and A1298C (Glu429A) are linked with RPL.
In this study, the effect of two factors, A4070G in FV and A1298C in MTHFR are evaluated in RPL patients from Mazandaran province, Iran.
Sample population of 100 women with RPL and 100 controls with Mazandarani ethnics from northern Iran were consist. The factor V (A4070G) and MTHFR (A1298C) polymorphisms were genotyped by PCR-RFLP.
Molecular study showed 5 women from patients and 9 women from control group were heterozygous AG for A4070G. Frequency of "A" allele in patient and control groups was 97.5% (0.975) and 95.5% (0.955) respectively, and "G" allele frequency was 2.5% (0.025) and 4.5% (0.045) respectively. No significant association (p≤0.05) between FV A4070G genotype and RPL with an OR=1.88, CI 95%=0.6-5.82, was observed (p=0.4). Also, for A1298C, all patients and control individuals were AA genotype. "A" allele frequency in patients and control was 100% and "C" allele frequency was zero. There was no significant difference for A1298C between groups.
Our finding showed that A4070G and A1298C polymorphisms cannot be considered as a cause of PRL in women from Mazandaran province, northern Iran.
To study the forensic application of Goldeneye DNA ID 26Y Kit in the She nationality.
Through capillary electrophoresis, the genotype of 26 Y-STR loci were analyzed in 53 unrelated male individuals ...from Fujian She nationality. The population genetics parameters such as allele frequency and haplotype diversity were calculated. The comparisons among the She nationality and the other nationalities were analyzed.
A total of 126 alleles were observed on the 26 Y-STR loci of 53 unrelated male individuals. The allele frequencies and GD value ranged from 0.010 1 to 0.886 8 and 0.211 2 to 0.846 2, respectively. The GD value was greater than 0.5 in the 19 loci. A total of 47 haplotypes were observed. Based on R(ST), multidimensional scaling plot indicated that the genetic relationship among Fujian She nationality and Minnan Han nationality was closest, followed by Southern China Han nationality and Northern China nationality.
Goldeneye™ DNA ID 26Y Kit including 26 Y-STR loci has good polymorphism in the She nationality
To determine the prevalence of most common mutations of cytochrome P450 (CYP), ie, allelic variants of CYP2C9, CYP2C19, and CYP2D6, and to predict genotype frequency in the Croatian population.
CYP ...genotype was determined in 200 non-related Croatian citizens. DNA isolated from blood samples was used for the analysis of the most common allelic variants of CYP2C9, CYP2C19, and CYP2D6 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
For 200 subjects genotyped for CYP2C9, the allele frequencies of CYP2C9*1 (wt), CYP2C9*2, and CYP2C9*3 were 0.74, 0.165, and 0.095, respectively. Among them, 3.5% of subjects were predicted to be poor metabolizers. For CYP2C19, the most frequent alleles were CYP2C19*1 and CYP2C19*2, with frequencies of 0.85 and 0.15, respectively; 3% of subjects were predicted to be poor metabolizers. For CYP2D6, the most frequent alleles were CYP2D6*1 (frequency 0.765), CYP2D62* (0.04), CYP2D6*3 (0.0275), CYP2D6*4 (0.14), CYP2D6*5 ( 0.01), and CYP2D6*6 (0.015). Out of these, 3% were predicted to be poor metabolizers, and 4% were predicted to be ultra-rapid metabolizers.
The prevalence of allelic variants and predicted genotypes in the Croatian population is in accordance with the other European populations, and it can be interpolated between the values for mid-European and Mediterranean populations.
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