MI is a complex multifactorial, polygenic disorder which results from the interaction between individual’s genetic makeup and various environmental factors. The principal pathogenesis of MI is the rupture of coronary atherosclerotic plaques. Recent studies have demonstrated the protective roles of SIRT1in inflammation processes, vascular endothelial homeostasis and ath- erosclerosis [20,35,36], providing evidence that SIRT1 may play an important role in the patho- genesis of MI. However, the association between SNPs inSIRT1gene and MI risk is still largely unknown. In the present study, we performed a genetic association analysis on the three SIRT1 tagSNPs (rs7069102, rs3818292 and rs4746720) in 287 MI patients and 654 controls. Our result showed that SIRT1 rs7069102 G allele is associated with a significantly increased risk of MI. We did not detect any association between rs3818292 and the risk of MI in allelic or genotypic analyses, which was in line with the previous report of rs3740051 (captured by rs3818292, r 2 = 1.0, S1 Table) in a Chinesepopulation . The haplotype (rs7069102G-rs3818292A- rs4746720T) containing the rs7069102 G allele also confers increased risk of MI. Further strati- fied analyses revealed that the increased risk of MI was more evident among younger subjects in allelic, genotypic or haplotypic analyses, but not among older subjects. The potential risk of MI in older individuals is more likely due to the aging effect (e.g., weak immune system, rela- tive high level exposure to environmental risk factors) rather than direct genetic effects. Thus,
A total of 291 AS patients and 312 healthy controls were recruited from The Third Affiliated Hospital of Zunyi Medical University. Both the patients and the controls were from a ChineseHanpopulation. The control population consisted of unrelated healthy individuals from the same geographical regions as where the AS patients came from, and they were age-, sex-, and ethnically matched with the patients. The patients with AS were diagnosed according to the New York modified criteria . The clinical characteristics of the AS patients were assessed at the time of diagnosis and summarized in Table 1. The study was approved by the local institutional ethics committee of The Third Affiliated Hospital of Zunyi Medical University. All procedures followed the tenets of the Declaration of Helsinki. Written informed consent was obtained from all the subjects. After obtaining the written informed consent, we took 5 ml of peripheral blood from each participant.
Other than the target genes, genes showing high dif- ferential expression included PTGS2, encoding a cyclooxy- genase that is a key enzyme in prostaglandin biosynthesis and is thought to be involved in the occurrence of myocar- dial infarction, hypertension, and diabetes. Studies have shown that polymorphism in the PTGS2 gene reduces the risk of myocardialinfarction and stroke by affecting COX- 2 activity and reducing the formation of atherosclerotic plaques (Cipollone et al., 2004). Relevant experiments have shown that the rs20417 mutant of the PTGS2 gene can significantly reduce the risk of cardiovascular events (Ross et al., 2014). Animal experiments have demonstrated that inhibiting PTGS2 expression can increase susceptibilityto salt-sensitive hypertension (Zhang MZ et al., 2015). The protein encoded by the PRKCI gene is one of the members of the protein kinase C family, which is known to affect glucose degradation by participating in insulin-mediated glucose transport (Bandyopadhyay et al., 2004). In the platelet activation pathway, the activated PRKCI protein activates the Ras-associated protein, RAP-1a, thereby indi- rectly promoting platelet aggregation. Among the screened genes, a large part has been found to be associated with tu- mor occurrence or participating in biological processes such as RNA degradation; yet not all genes were found to
Numerous studies have been conducted to explore the association of this ApoE polymorphism and CHD; some of the studies found a significant association between the ApoE e4 allele and CHD [15–17]. A meta-analysis conducted in 2004 provided evidence that the e4 allele of ApoE was a risk factor for the development of CHD . Another meta- analysis conducted in 2013 further confirmed this finding in a Chinesepopulation . However, no meta-analysis has been conducted to explore the association between this ApoE gene polymorphism and MI. In spite of the presence of advanced CHD, only a subset of patients develops MI during their life. The reasons for these individual differences insusceptibilityto MI are poorly understood. Therefore, it is important to explore the association between ApoE gene polymorphisms and MI. In fact, a number of case- control studies have been conducted to clarify the association between ApoE gene polymorphisms and MI [20–52]; however, the results are inconsistent. Therefore, we conducted this meta- analysis including all of the evidence produced to date to explore this issue.
c.335T.C was investigated using the created restric- tion site-PCR (CRS-PCR) method with one of the primers containing a nucleotide mismatch, which enables the use of restriction enzymes for discriminating sequence variations (33-35). c.3073A.C was detected by the PCR-restriction fragment length polymorphism (PCR-RFLP) method. Following the supplier’s manual, 5-mL aliquots of PCR- amplified products were digested with 2 U restriction enzyme at 37 6 C for 10 h. The digested products were separated by 2.5% agarose gel electrophoresis and observed directly under UV light in order to determine the genotype of MDR1 polymorphisms. To confirm the geno- type results obtained by CRS-PCR and PCR-RFLP, about 20% of PCR-amplified products were randomly selected for DNA sequencing (TaKaRa Biotechnology Co., Ltd., China).
Data in this study are electronic medical records (EMR) from hospital information system (HIS) from 17 hospitals (including both Western Medicine (WM) and Traditional Chinese Medicine (TCM) hospitals) in China, which were standardized and integrated into a central- ized data warehouse by Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science. All the 17 hospitals are level 3 institutions (major tertiary referral centers in provincial capitals and major cities) , which spread across 7 different provinces, including Beijing, Shenzhen, Guangdong, Shanxi, Fujian, Hebei and Jilin. There is a total of 2.42 million inpatients in the database, which was collected longitudinally from 2002 to 2011. It should be noted that in China, HIS were gradually implemented after 2005. In the 17 hospi- tals of our data warehouse, only one hospital has data between 2002 and 2004, so we did not in- clude the data during this period for analysis. The majority of hospitals started to implement HIS in 2007 in our database, so the number of patients before 2007 were relatively smaller.
Glutathione S-transferase P1 (GSTP1) is a critical enzyme in the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is ARG at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site and reduced catalytic activity. We evaluated the interaction between GSTP1 Val allele and Helicobacter pylori infection, smoking and alcohol consumption, increasing the risk of gastric cancer among the Chinesepopulation. Information on potential gastric cancer risk factors and blood specimens were collected from 618 incident gastric cancer cases and 1,830 non-cancer controls between March 2002 and December 2011 in Liaoning Province, China. GSTP1 Ile105Val was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism. Serum levels of anti-H. pylori IgG were measured by ELISA. Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate logistic regression, adjusted by sex and age. The risk of gastric cancer was significantly elevated in patients with the GSTP1 Val/Val genotype (adjusted OR = 3.324; 95% CI = 1.790–6.172). An elevated risk of gastric cancer was observed in patients with H. pylori infection, smoking, or alcohol consumption, and together with the GSTP1 Ile/Val +Val/Val genotype (OR = 3.696; 95% CI = 2.475–5.521; OR = 1.638; 95% CI = 1.044–2.571; OR = 1.641; 95% CI = 0.983–2.739, respectively) (p,0.05). The GSTP1 Val allele shows an interaction with smoking, alcohol consumption, and especially H. pylori infection for increasing the risk of gastric cancer. These findings could demonstrate new pathophysiological pathways for the development of gastric cancer.
An important source of bias in every meta-analysis is related to the studies that have been published and thus can be included in the analysis. Nevertheless in our meta-analysis, we included many studies with negative findings. Although the funnel plot for G49A polymorphism is not symmetric, the overall results of different ethnic groups are concordant, indicating that this bias cannot affect the final result. On the other hand, funnel plot asymmetry is not always caused by publication bias. True heterogeneity may also lead to funnel plot asymmetry. For example, significant difference may be seen only in high-risk individuals, and these high-risk people are usually more likely to be included in small studies. This is particularly true in our meta-analysis because the majority of the significant associations have been observed among the studies with small sample size. Language bias or citation bias also could be an important source in this group of studies, meaning that the studies without significant findings are preferentially published in languages other than English and less likely to be cited in other articles. Finally, it is possible that an asymmetrical funnel plot arises simply by chance.
Numerous factors have been reported to influence the results of the study on the association of gene polymorphisms with disease. We made the following efforts to ensure correctness of the results. The ocular BD patients were selected strictly according to the criteria of the International Study Group or the revised criteria from Behcet’s Disease Research Committee of Japan if oral ulceration was not present, and two cohorts of the samples came from two independent uveitis centers in China. The healthy individual controls were recruited from the same geographical regions as the patients. No statistical differences were observed in the distribution of age and gender for the collected ChineseHan case-control cohorts. In order to validate the results of genotyping by PCR-restriction fragment length polymorphism, 10% of the samples were randomly chosen and confirmed by direct sequencing.
Compared with Europe population, there is a rather small genetic diversity inChineseHanpopulation . Despite all that, Pritchard  illustrated that small diversity may be sufficient to lead to an inflated rate of false-positive results. In other words, the intricate substructure of HanChinese may cause spurious association between polymorphism and T2DM risk. Xu  showed that there was the greatest genetic differentiation of ChineseHanpopulation between the northern HanChinese (NHC) and the southern HanChinese (SHC) based on the genetic boundary of Yangtze River. Therefore, it is necessary to evaluate the effect of population substructure on the association between SNP of TCF7L2 and T2DM risk. A subgroup meta-analysis was utilized to explore the effect of the population substructure on the overall estimation of the association. Our analysis indicated that there was no association between SHC and NHC. On the other hand, the analysis result also reflected the heterogeneity among the included studies by heterogeneity test. We found that this Figure 10. Forest plot of the association between rs290487 T/C polymorphism and T2DM risk (subgroup analyses for the HWE in the control groups: C vs. T). n indicates the total number of C allele, and N indicates the total number of C allele plus G allele.
In the biogenesis of miRNAs, the Argonaute proteins (Ago1-4) along with Gemin3 and Gemin4 selectively bind to the guide strand to facilitate the formation of an miRNA- RNA-induced silencing complex (RISC) (Slaby et al., 2012). Single nucleotide polymor- phisms (SNPs) may be present in miRNA-binding sites, and mature miRNAs negatively regulate the expression level of their target genes via two distinct mechanisms (Bartel, 2004). In the first mechanism, miRNAs block target gene expression at the translational level with imperfect complementarity. In the second mechanism, miRNAs bind to their mRNA targets with perfect (or nearly perfect) complementarity to induce the RNA- mediated interference pathway (Esquela-Kerscher & Slack, 2006) (Fig. 1). Alterations in the miRNA biosynthesis pathway can lead to global miRNA deregulation. Because miRNAs are involved in a wide range of developmental and physiological processes, deregulation of miRNA processing pathways could potentially impact the transcription and splicing of miRNAs as well as the transcriptional regulation of genes that play funda- mental roles in cancers and/or many other human diseases (Kim et al., 2010; Melo & Melo, 2014). Since the impairment of mature miRNAs is emerging as a feature of human cancers (Sonia et al., 2010), given the critical function of Gemin3, Gemin4 and Ago1-4 in miRNA biosynthetic pathway. The host genomic polymorphism of those genes may represent keydeterminants of cancers. SNPs that deregulate miRNAs may alter the expression level of genes related to disease susceptibility (Horikawa et al., 2008; Liu et al., 2012a). Although several studies have investigated the association between the Gemin3 rs197412 T > C, Gemin4 rs7813 T > C and rs2740348 G > C polymorphisms with cancer susceptibility, the results were contradictory and uncertain. Hence, a metaanalysis based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria (Moher et al., 2009) was imperative to assess the associations between cancer susceptibility and the Gemin3 rs197412, Gemin4 rs7813 and Gemin4 rs2740348 polymorphisms.
very elderly individuals comes from the possibility that there could be less variability of important predicting values within a very advanced age range. For instance, the uniformity of advanced age in this sample may deprive this variable of its discriminatory power, which would not depict great contrast among the individuals. The inclination of this risk function may be lower when there are only very elderly patients. The same may occur with other variables which may be systematically altered in a very elderly sample. Also, the calibration of the score in estimating the numerical risk of death may be different for these patients, once the alpha constant (intercept) tends to be greater in samples with the highest risk. This could explain the need for recalibration of the score.
A total of 1,080 AD patients and 908 controls were enrolled in this study (Table 1). All samples were from the ChineseHanpopulation and were used in our previous GWAS. AD patients meeting the Hanifin-Rajka diagnostic criteria  were recruited from the No. 1 Hospital of Anhui Medical University and the Xinhua Hospital affiliated with the Shanghai Jiaotong University School of Medicine in China. Physician specialists collected clinical data from the affected individuals through a full clinical checkup. Additional demographic information was collected from the cases and controls through a structured questionnaire. The disease severity was evaluated using the objective SCORing Atopic Dermatitis (SCORAD) index , which categorizes patients as mild (#15 points), moderate (15–40 points) and severe (.40 points). Patients were considered to have food intolerance either evaluated by allergen test of venous blood samples or patients’self- reports. All controls were clinically assessed to be without AD or other atopic diseases, a family history of atopic diseases (including first-, second- and third-degree relatives) or ichthyosis vulgaris (IV). All participants provided written informed consent. The study was approved by the Institutional Ethics Committee of Anhui Medical University and was conducted according to the Declaration of Helsinki principles.
In conclusion, our data have diferent frequency of HLA alleles in Southern Brazilian population than the previous published with the Southeast Brazil region and Europeans. We also specu- late that further studies of HLA regarding the MS susceptibilityin the European Countries in the next century may ind diferent re- sults from today when using high resolution techniques and large control groups. We do not know the efect of the dilution of the original HLAs alleles due to the massive immigration which is oc- curring in the present days, similar that occurred with the original Brazilians inhabitants over the last 500 years.
Zimmerman (1999) in his article titled ―Mobile Computing: Characteristics, Benefits, and the Mobile fra mework‖ defined mobile computing as ―the use of computing devices, which usually interact in some way with a centralised information system while away from the normal fixed workplace‖. He went on to say that, Mobile computing technology enables the mobile person to create, access, process, store and communicate information without being constrained to a single location. It is on the above basis that this researcher views mobile computing as embracing a host of portable technologies the can access internet using wireless fidelity (WIFI). These range from notebook computers to tablets, to smartphones and e-book readers. Such devices have brought about Mobile learning (m-Learning) in Zimbabwe Polytechnics, enabling staff and students to share academic resources, be able to research and develop applications from wherever they are. Zimmerman (1999) went on to identify mobile computing hardware, software and communications in use then. He identified hardware as palmtops, clamshells, handheld Pen Keys, pen slates, and laptops. The characteristics of such devices in terms of screen size was small, processing capability was limited and supported a few mobile applications. Over the years mobile devices have improved in such characteristics to make mobile computing easy, fast and user friendly. Great improvements also came with the associated systems software, with the modern devices now running on Android, Symbian and windows 8 mobile, as compared to then when MS DOS, Windows 3.1, Pen DOS were used. In communications Zimmerman talked of internet speeds in kilobytes per second (Kbps), while today’s communications devices have speeds of gigabytes per second (Gbps
Compared with other studies, ours was the first to investigate the association between the functional hOGG1 Ser326Cys poly- morphism and NIHL risk. Moreover, thousands of workers who had been exposed to steady noise for up to 20 years or more but who were less exposed to other occupational hazards were enrolled in our study. Furthermore, all of our NIHL workers were in an early stage of NIHL according to GBZ49-2002; additionally, individual noise meters were used to assess the noise environment so that the results would reflect real exposure levels. One limitation of this study was that the NIHL workers with both low- and high- frequency hearing ranges worse than 25 dB were all transferred from noisy environments; therefore, selection bias may exist in our study.
Triple-negative breast cancer (TNBC) is defined by the lack of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). It is characterized by aggressive behavior, poor prognosis and lack of targeted therapies. MicroRNA (miRNA) as a novel modulator of gene expression has played an important regulatory role in the malignancy. Dysregulation and/or mutation of the miRNAs may also contribute to the TNBC susceptibility since it is associated with the expression of ER, PR and HER2. Single nucleotide polymorphisms (SNPs) in miRNAs may be extremely relevant for TNBC. We tried to validate the hypothesis that genetic variations in miRNA are associated with TNBC development, and identify candidate biomarkers for TNBC susceptibility and clinical treatment. We screened the genetic variants in all miRNA genes listed in the public database miRBase and NCBI. A total of 23 common SNPs in 22 miRNAs, which tagged the known common variants in the ChineseHan people with a minor allele frequency greater than 0.05, were genotyped. This case-control study involved 191 patients with TNBC and 192 healthy female controls. Frequencies of SNPs were compared between cases and controls to identify the SNPs associated with TNBC susceptibility. No significant association was found between TNBC risk and the SNPs in the miRNA genes in the ChineseHan people (P.0.05), but this warrants further studies.
This case-control study has several potential limita- tions that merit careful consideration. First, the patients and controls recruited from hospitals may not be represent- ative of the general population. Nonetheless, the genotype distribution of the controls was in HWE. Second, because of the limited sample size, a single case-control study may be insufﬁcient to fully uncover the relationship between the AIRE rs878081 polymorphism and susceptibilityto RA. Thus, our ﬁndings should be conﬁrmed by larger numbers of subjects. Third, we did not obtain detailed information about RA severity and response to treatment, which restricted our analyses. Fourth, the risk of RA cannot be attributed to a single AIRE gene SNP, but should be interpreted by considering other AIRE SNPs, other genes, and some environmental factors. Fifth, the underlying mechanisms of this SNP in RA were not investigated. Finally, the true signiﬁcance of the association between this SNP and RA risk should be validated by further studies in different populations.