International journal of molecular epidemiology and genetics最新文献

CYP2C9 gene encodes an enzyme involved in the metabolism of a wide variety of drugs which include celecoxib. This study investigated the frequencies of the alleles and genotypes of CYP2C9*1, CYP2C9*2, and CYP2C9*3 among Filipinos who underwent surgery, and to determine the association of CYP2C9 polymorphisms with post-operative pain relief via COX-2 inhibitors. Response to celecoxib was determined using the numerical rating scale (0-10) on the 24th and 48th hour of surgery. The CYP2C9 alleles were detected by real-time PCR. For CYP2C9*1 and CYP2C9*3, the allele frequencies among Filipinos were 99% and 1% respectively, which is similar with other East Asians. CYP2C9*2 alleles were not detected. The frequencies of CYP2C9*1/*1 and CYP2C9*1/*3 genotypes were 98% and 2% respectively. At 24 hours post-surgery, the average pain score was 2.57 ± 1.03, while on 48 hours post-surgery, the average pain score was 0.67 ± 0.61 among those who have the wild-type CYP2C9*1 allele. The average pain score on the 24th and 48th hour post-operatively was observed to be 2.5 ± 0.71 and 0.5 ± 0.71 respectively among two patients classified as intermediate metabolizer carrying the CYP2C9*1/*3 genotype. Low frequencies of CYP2C9 polymorphisms were observed in the present study, this pattern was similar with other Asians except Indians, and considerably lower than Caucasians. Our results suggest that CYP2C9 genotyping is not routinely needed for Filipinos but must be considered among mixed races. Consequently, a more personalized therapeutic strategy was derived from these data, resulting in good clinical outcomes and less adverse drug effects.

Triple negative breast cancer account for 10% to 20% of all newly diagnosed breast cancer cases, this subtype is well known for its lack of estrogen, progesterone and HER2 expression unlike the other subtypes of breast cancer that usually express at least one of the three. The absence of a specific biomarker for TNBC has made his treatment very challenging and his death rates very high compared to the other subtypes. Therefore, in morocco, many studies have been conducted in the hope of finding a specific biomarker for TNBC, but none of these studies has analyzed the EGFR protein expression and its gene molecular profile and correlated the EGFR analyses results with the genetic profile of other genes. In this study, we analyzed EGFR protein expression and the molecular profile of EGFR, BRCA1, BRCA2 and TP53 genes in 47 TNBC patients. We conducted a retrospective study of 47 Moroccan patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we have analyzed the EGFR. Protein expression, for all the 47 TNBC patients using pharmDx Kit. Then we used the Ion Personal Genome Machine (PGM) and Ion Ampliseq BRCA1/2 panel and hotspot Cancer panel to analyze the molecular profile of BRCA1/2 genes and the hotspot regions of TP53 and EGFR genes. The statistical analysis was performed using IBM SPSS Statistics ver. From the 47 analyzed patients using EGFR pharmDx Kit only 16 (34%) had EGFR overexpression while 31 (66%), patients were normal, moreover, From the 47 TNBC patients, only 39 underwent Mutational analysis of EGFR, BRCA1/2, and TP53 genes. One patient harbored a BRCA1 mutation c.798_799delTT (p.Ser267Lys). While for TP53 gene, 16 patients out of 39 (41%) presented hotspot mutations, seven of them harbored c.743G>A (p.Arg248Gln) mutation, six patients harbored exon 6 mutations from which five harbored the mutation c.659A>G (p.Tyr220Cys) and one the mutation c.817C>T (p.Arg273Cys), and finally, three patients harbored the mutation c.524G>A (p.Arg175His). Regarding BRCA2 and EGFR sequencing results, no mutations or other genetic alterations were detected in 39 patients that were successfully sequenced. Statistical analysis revealed the absence of any correlations.

Background: Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC) and remains a serious global public health threat, especially in resource-limited settings such as the African region. Recent developments in molecular epidemiology tools have significantly improved our understanding of TB transmission patterns and revealed the high genetic diversity of TB isolates across geographical entities in Africa. This study reports the results of a systematic review of current knowledge about MTBC strain diversity and geographical distribution in African regions.

Methods: Search tools (PubMed, Embase, Popline, OVID and Africa Wide Information) were employed to identify the relevant literature about prevalence, strain diversity, and geographic distribution of MTBC infection in Africa.

Results: A total of 59 articles from 739 citations met our inclusion criteria. Most articles reported about patients with presumptive pulmonary TB (73%), fewer reports were on retreatment and treatment failure cases (12%), and presumptive drug resistance cases (3%). Spoligotyping was the most used, alone in 21 studies and in parallel with either the Mycobacterial Interspersed Repetitive Units Variable Number of Tandem Repeats or the Restriction Fragment Length Polymorphism. Various TB lineages were observed across the African continent, with the originally European lineage 4 spotted in all countries studied.

Conclusion: TB molecular epidemiology tools have substantially improved our understanding of the MTBC circulating isolates, their evolution, and diversity in this highly endemic region of Africa. We found that only TB lineage 4 is present throughout all the continent and the clusters identified provides an extended insight into the disease transmission dynamics.

Cigarette smoking can increase the risk of many respiratory and chronic systemic diseases. Particularly, cigarette smoke produces toxic particulate matter (PM), which is harmful to the smokers. Although previous studies have demonstrated the toxicity of cigarette smoke PM and its relationship with disease pathogenesis, systematic data for the impact of cigarette smoke PM on physical activity and metabolism in animals are still lacking. In this report, the C57/B6 mice were exposed to cigarette smoke PM in a smoking chamber coupled with the analysis of metabolic changes and physical activity in metabolic cages at indicated time, for a period up to 12-month-old of age. The mice became excited following short period (e.g., 3 months) but listless after long-term cigarette smoke PM exposures (e.g., 9 or 10 months), as manifested by the changes of drink/food intake and daily activities along with increased oxygen consumption and CO₂ accumulation. Our data suggest that particulate matter originated from cigarette smoke impairs metabolism and physical activities.

Studies have shown association of lipoprotein lipase (LPL) polymorphisms with coronary artery disease (CAD); however, limited studies on the genetics of CAD have been done in the Philippines. Because of their effects on high-density lipoprotein and triglyceride metabolism, the G-allele of the Ser447X variant of LPL gene has been shown to be atheroprotective, while HindIII polymorphism has been shown to be pro-atherogenic. We assessed 1301 patients undergoing coronary angiography to determine the prevalence of HindIII and Ser447X polymorphisms and their association with angiographically significant CAD. Genotyping for HindIII and Ser447X variants were analyzed by real-time PCR. Multivariate analyses were performed to determine the interaction between LPL polymorphisms and risk factors of CAD. CAD+ group (72%) was predominantly male (76%) with a mean age of 60.17 ± 11.01 with hypertension (89%), dyslipidemia (84%) and smoking (54%) as the most common risk factors. HindIII carriage frequency among the CAD+ group was 20.3% with a genotypic distribution of 78.71% (T/T), 19.83% (T/G) and 1.46% (G/G). Ser447X carriage frequency among the CAD+ group was 8.0% with a genotypic distribution of 91.39% (C/C), 8.38% (C/G) and 0.23% (G/G). HindIII and Ser447X polymorphisms were both not significantly associated with CAD. LPL polymorphic allele HindIII was common, while Ser447X was rare. Present study did not show association of LPL polymorphisms with the development of CAD. However, among patients with dyslipidemia, presence of Ser447X allele is associated with an increased risk (OR 2.6; 95% CI 2.1-3.7; p value < 0.001) of developing CAD than those without LPL polymorphisms.

In recent years, cardiovascular diseases (CVDs) have become a focus topic and global concern. There have been mixed reports on the relationship between whole grain or cereal fiber intake and the risk of type 2 diabetes. To evaluate whole grain or cereal intake on the risk of type 2 diabetes, we collected related literature on the relationship between whole grain or cereal fiber intake and the risk of type 2 diabetes. Methods: Eligible studies were identified from PubMed, Web of Science, and EBSCO (from 2007 to 2015). A total of three studies on whole grains were included, three studies about cereal fiber, and two on both whole grains and cereal fiber. We calculated the summary relative risks (RRs) using the random effects model. Eight studies contained 14,728 type 2 diabetes cases out of 434,903 subjects. Whole grain or cereal fiber intake is associated with type 2 diabetes (the overall RR was 0.68; 95% CI was 0.64-0.73) with significant heterogeneity in study-specific estimates (I² =0%, P=0.452). Whole grain and cereal fiber intake are inversely associated with the risk of type 2 diabetes.

Acute respiratory tract infections are common worldwide and caused by a great diversity of pathogens. A rapid and accurate diagnosis method of respiratory infection is crucial for timely clinical intervention. Here, by combining fluorescence melting curve analysis and multiplex real-time assay, we developed a novel method which can simultaneously detect 15 respiratory viruses. The specificity for target genes was 100%, as assessed with a panel of 47 respiratory pathogens, which indicated no cross-reactions. The assay's limits of detection at the nucleic acid level ranged from 5 copies/μL to 500 copies/μL nucleic acids. Compared with conventional culture method, our assay showed more than 75% sensitivity and 100% specificity for each respiratory pathogen in 384 clinical samples. Even more, the kappa correlation for all the pathogens ranged from 0.86 to 1.00. Overall, this method has the characteristics of high throughput, low cost and high sensitivity and precision, which demonstrated our method is well suited for routine clinical testing in respiratory infection.

The T-cell response and tolerance in non-lymph tissues differs from those in lymph tissues such as the spleen and thymus. The distribution and composition of the TCR repertoires in non-lymph tissues and how they differ and associate with their counterparts in lymph tissue remain unclear. Thus, we studied the thymus, spleen, blood, liver and small intestine of BALB/c mice at the ages of one, three and five months to carry out a preliminary analysis of the spatial-temporal homogeneity and heterogeneity of the total TCR β chain CDR3 repertoire using high-throughput sequencing technology and immune bioinformatics approaches. The data show that the diversity of the CDR3 repertoires was decreased as the mouse age increased, except in the small intestine. The number of low-expanded clones in the CDR3 repertoires was greatest in the thymus, followed by the spleen, blood, liver and small intestine, and highly expanded clones had an opposite trend in the different mice ages. The thymus and the spleen showed the greatest overlap of CDR3 sequences with the other tissues across the different mice ages. The distribution of the CDR3 repertoire length was normal, with a median of 14 aa in all the mouse tissues, except the small intestine of the one-month-old mice had a median of 12 aa. In summary, the composition and characteristics of the CDR3 repertoires in the thymus were similar to those in the spleen, and repertoires in the blood were similar to those in the liver; only the small intestine showed a unique composition. These results offer a novel method to explore the source, differentiation, proliferation and response of distinct T cells in different tissues at different mice ages.

Background: In genome-wide studies, there is a strong association between the TMPRSS6 allele A736V (rs855791) and significantly lower levels of serum iron, transferrin saturation, haemoglobin, and mean corpuscular volumes. The influence of this genetic variant on susceptibility to iron deficiency anaemia (IDA) in chronic kidney disease (CKD) patients is unknown.

Methods: In this cross-sectional study, we measured the full blood count and TMPRSS6 T>C polymorphism in black adult participants (n=260) with CKD and healthy controls (n=146) at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa.

Results: The overall prevalence of anaemia in the CKD and control population was 46.9% and 19.6% respectively. Twenty-six per cent of CKD participants were iron deficient. The prevalence of rs855791 C homozygosity was similar among iron deficient and non-iron deficient anaemia groups (86.1% vs 84.2%, P=0.723). When the analysis was confined to subjects with or without functional iron deficiency anaemia, C homozygote (88.3% vs 84.4%, P=0.425) was similar for both groups.

Conclusions: Our study suggests that homozygosity for TMPRSS6 rs855791 C genotype does not influence IDA in non-dialysis CKD patients in our population.

Aims: To investigate the distribution of vitamin D receptor fokI gene polymorphism in Yunnan Han population, and to explore the relationship between SNP of fokI and type 2 diabetic kidney disease.

Methods: We included 276 individuals of Han population of Yunnan in this study: 91 type 2 diabetes patients without kidney disease (DM group), their duration of diabetes is more than 10 years, 89 type 2 diabetes patients with diabetic kidney disease (DKD group), their duration of diabetes is less than 10 years and 96 healthy controls (NC group). We compared the concentration of 25 hydroxy vitamin D in different groups and used taqman probe to detect the genotype and allele of fokI, then analysed the relationship between the polymorphisms of fokI and the susceptibility of diabetic kidney disease.

Results: (1) NC group had a significantly higher plasma concentrations of 25 (OH) D than DKD group and DM group (P < 0.01); (2) 25 (OH) D and age, BMI, HbA1c, TG showed a weak negative correlation (P < 0.01); (3) Genotype of fokI showed no differences in DM group and DKD group, same as in DM group and NC group; FF genotype in DKD group is relatively lower than NC group (P < 0.05), and there is no difference in Ff and ff genotype (P > 0.05); In DKD group, f allele was 53.4%, higher than DM group (RR = 1.46, P < 0.05); (4) Logistic regression analysis showed that ff genotype may be a susceptible factor for DKD (P = 0.04, OR = 2.37).

Conclusion: FokI Ff genotype accounted for a larger proportion of the Han population in Yunnan, and ff genotype may be a susceptible factor for DKD in Yunnan Han population.