Family Susceptibility Research Articles

Association between MEF2 family gene polymorphisms and susceptibility to multiple sclerosis in Chinese population.

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Myocyte enhancer factor 2 (MEF2) family genes play important roles in the immune response. This study focuses on the relationship between MEF2 family gene polymorphisms and MS. A total of 174 MS patients and 120 healthy controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the gene polymorphisms of MEF2D and MEF2C. In addition, peripheral blood was collected and leukocytes were isolated. The transcription level of MEF2D in the two groups of samples was detected with quantitative real time polymerase chain reaction (qRT-PCR). We found that the C allele frequency and CC genotype frequency of rs2274316 in MEF2D were significantly higher in MS patients. The C allele and CT genotype distribution for rs3790455 were significantly more frequent in MS patients. Female patients showed higher CC genotype frequency of rs2274316. The genotype frequency distribution of rs2274316 and rs3790455 were not related to onset age and phenotype of MS patients. In addition, this study also proved that MEF2D was significantly overexpressed in the peripheral blood leukocytes of MS patients. The transcription level of MEF2D was significantly higher in patients with CC genotype of rs2274316. These findings suggest rs2274316 and rs3790455 of MEF2D gene are potential genetic risk factors for MS in Chinese population. The transcription level of MEF2D is also associated with susceptibility to MS and MEF2D gene polymorphisms.

Sarcoidosis in Close Family Members and Susceptibility to High Grade B-Cell Lymphoma: A Case Report Study

The presented case is an 81- year-old woman who had experienced episodes of facial twitching without loss of consciousness and flu like symptoms for a few weeks prior to her admission. examinations were unremarkable except for left 3rd nerve and right 6th nerve palsy, right peripheral facial palsy and right -side hemiparesis. FH was positive for sarcoidosis. neuroimaging were in favor of PCNSL.
 Sarcoidosis and malignancy maybe etiologically related in at least 25% of cases. Coexis- tence of sarcoidosis and lymphoma have been reported previously. Our patient had two daughters with sarcoidosis and her chest CT scan showed multiple lymph nodes inmedias- tinum. Unfortunately, due to the location and the technical restriction, biopsy of mediasti- nal lymph nodes was not performedfor our patient and we could not differentiate whether it was reactive, paraneoplastic or granulomatous. We present this case as concurrence of lymphoma and sarcoidosis in a family, which could guide a new concern for the patient with granulomatous infiltrative disease for early diagnosis and familial screening.

Abstract 11802: Evaluation of Family Risk of Rheumatic Heart Disease With Systematic Echocardiographic Screening: Data From the Provar+ Study

Introduction: Rheumatic Heart Disease (RHD) is determined by a complex interaction between socioeconomic environment and host susceptibility. Relatives of patients with advanced RHD share both, and may be at high-risk. We aimed to use echocardiographic (echo) family screening to evaluate the risk of RHD among 1 st degree relatives of patients with advanced RHD. Methods: From Feb 2020 - Jun 2021 patients with advanced RHD were consecutively enrolled in the University Hospital’s outpatient clinics. Consented 1 st degree relatives were invited for echo screening (2012 World Heart Federation Criteria) utilizing handheld devices (GE VSCAN) by non-physicians, with telemedicine interpretation by 2 experts. Matched controls (spouses, neighbors) living in the same household were also enrolled in a 1:5 fashion. A confirmatory full echo (GE Vivid IQ) was scheduled if abnormalities were observed, and all positive RHD cases were referred for follow-up. Results: In 16 months, 202 relatives and 42 controls of 117 patients were screened, including 114 children, 68 siblings and 20 parents. Mean age was 41±18 years, 62% were women and 214 (88%) lived with the index case for >10 years. At total 51 (21%) individuals had hypertension, 17 (7%) diabetes, 5 reported a previous stroke and only 5 (all relatives) had personal history of RHD. Among index cases, 73% reported current or past prescription of Penicillin. Echo findings suggestive of RHD were observed in 0 controls and 14 (7%) relatives (p=0.08), being 11 with mitral valve (MV) disease and 3 with mixed (mitral and aortic valve (AV)) disease. Eleven patients had mild/moderate MV regurgitation, 4 with associated MV stenosis and abnormal morphology. Two patients had mild AV regurgitation and abnormal AV morphology, associated with mild AV and MV stenosis, and 1 patient had bioprostheses in the MV and AV. One case of mild left ventricular dysfunction was observed, and 1 patient had indication of commissurotomy for MV stenosis at the time of diagnosis. Conclusions: First-degree relatives of individuals with clinical RHD are at greater risk of having RHD and family screening should be considered. Genotyping studies are warranted to better understand individual and family susceptibility to RHD, in addition to socioeconomic conditions.

Novel Roles of the Tim Family in Immune Regulation and Autoimmune Diseases

T cell Ig and mucin domain (Tim) protein family members were identified to be important regulators of the immune response. As their name indicates, Tim proteins were originally considered a T cell-specific markers, and they mainly regulate the responses of T helper cells. However, accumulating evidence indicates that Tims are also expressed on antigen-presenting cells (APCs), such as monocytes, macrophages, dendritic cells (DCs) and B cells, and even plays various roles in natural killer cells (NKs) and mast cells. In recent years, the expression and function of Tims on different cells and the identification of new ligands for the Tim family have suggested that the Tim family plays a crucial role in immune regulation. In addition, the relationship between Tim family gene polymorphisms and susceptibility to several autoimmune diseases has expanded our knowledge of the role of Tim proteins in immune regulation. In this review, we discuss how the Tim family affects immunomodulatory function and the potential role of the Tim family in typical autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D). A deeper understanding of the immunoregulatory mechanism of the Tim family might provide new insights into the clinical diagnosis and treatment of autoimmune diseases.

Association between ABC family variants rs1800977, rs4149313, and rs1128503 and susceptibility to type 2 diabetes in a Chinese Han population.

ObjectiveTo investigate the association between three single nucleotide polymorphisms (SNPs) of the ATP-binding cassette (ABC) gene family and susceptibility to type 2 diabetes mellitus in a Chinese Han population.MethodsA total of 1086 type 2 diabetes patients and 1122 healthy controls were included in this retrospective study. Three genetic variants, rs1800977 and rs4149313 in ABCA1, and rs1128503 in ABCB1 were included in the study. Susceptibility to type 2 diabetes was evaluated under three genetic models.ResultsA significant association between rs1800977 and type 2 diabetes was identified in three different genetic models (TT vs CC, odds ratio [OR] = 0.611 [95% confidence interval (CI), 0.469–0.798]; T vs C, OR = 0.841 [95% CI, 0.745–0.950]; and the recessive model, OR = 0.606 [95% CI, 0.474–0.774]). Additionally, a significant association between rs4149313 and type 2 diabetes was identified in three different genetic models (AA vs GG, OR = 0.467 [95% CI, 0.326–0.670]; A vs G, OR = 0.819 [95% CI, 0.717–0.935]; and the recessive model, OR = 0.478 [95% CI, 0.336–0.680]).ConclusionWe found that SNPs rs1800977 and rs4149313 in ABCA1 are significantly associated with susceptibility to type 2 diabetes in a Chinese population, although this should be confirmed in a larger study.

Association Study of the Caspase Gene Family and Psoriasis Vulgaris Susceptibility in Northeastern China.

Background Abnormal apoptosis of keratinocytes is one of the pathological changes of psoriasis. Caspases (CASPs) are the central engines of apoptosis. Studies to date have shown that some SNPs alter the expression of related genes and lead to changes in disease risk. However, no studies have investigated the associations between gene polymorphisms and the risk of psoriasis in Han population in northeast China. Therefore, we conducted a case-control study to explore this question in Han population of northeastern China. Methods 540 patients with PsV and 612 healthy age- and sex-matched controls were enrolled in this study. We determined the genotypes of 17 single nucleotide polymorphisms (SNPs) from 11 genes of caspase family by the improved multiplex ligation detection reaction (iMLDR) method. A model-based single SNP frequentist test and haplotype association studies were performed to evaluate the association between SNPs and PsV. Results In the single SNP tests, rs6704688 in CASP8 was significantly associated with psoriasis vulgaris (PsV) in Han population of northeastern China (P = 0.0169, P' = 0.0179 under the additive model; P = 0.0126, P' = 0.0149 under the heterozygous model). In haplotype analyses, the CASP7 haplotype GC was found to be associated with PsV risk (case group versus control group, 47.2% versus 54.4%, respectively, p = 0.0149). Conclusions Our study presented that the gene polymorphisms of CASP7 and CASP8 were significantly associated with PsV in Han population of northeastern China, which implied the functional relationship between PsV and caspase genes. CASP8 and CASP7 SNPs could be new potential biomarkers for risk stratification and prevention of PsV.

TIM family gene polymorphism and susceptibility to rheumatoid arthritis: Systematic review and meta-analysis.

BackgroundTIM-family proteins are expressed on different immune cells such as dendritic cells, macrophages, type 1 and 2 T helper (Th) cells. Therefore, they have the ability to contribute to the various intracellular signals and immune responses, importantly the regulation of Th1 and Th17 cell differentiation, which plays a remarked role in fight against inflammatory and autoimmune diseases. Association of TIM family gene polymorphisms with rheumatoid arthritis (RA) has been frequently investigated. The findings however are not entirely consistent. Therefore, we carried out the present meta-analysis to examine the association between RA and the following TIM family gene polymorphisms: rs41297579, rs1036199, rs10515746, and rs7700944.MethodsA systematic search of Scopus, PubMed, and Web of Science databases was conducted through December 2018. Combined odds ratios (OR) with their corresponding 95% confidence intervals (CI) were calculated under different possible genetic models.ResultsA total of eight case-control studies were included in the present meta-analysis. The results demonstrated significant association of RA with TIM-3 rs1036199 polymorphism under dominant (OR, 1.93, 95% CI, 1.43–2.61) and allelic models (OR, 1.74, 95% CI, 1.31–2.30). None of the other examined polymorphisms indicated significant association with RA.ConclusionsThe present meta-analysis revealed that the TIM-3 rs1036199 polymorphism might confer susceptibility to RA. Further studies are required to reassert our findings.

Genetic variants of SMAD2/3/4/7 are associated with susceptibility to ulcerative colitis in a Japanese genetic background

PurposeInflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is attributed to inappropriate inflammatory response in intestinal mucosa. Transforming growth factor β (TGF-β)/SMAD signaling plays key role in differentiation of naïve CD4+ T cells to T helper 17 (Th17) cells or regulatory T (Treg) cells. This study aimed to investigate associations between single nucleotide polymorphisms (SNPs) of SMAD family genes and susceptibility to IBD in a Japanese cohort to elucidate genetic determinants of IBD. MethodsThis study included 81 patients with CD, 108 patients with UC, and 199 healthy subjects as controls. A total of 21 SNPs in four genes (SMAD2, SMAD3, SMAD4, and SMAD7) involved in the TGF-β/SMAD signaling pathway were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR-direct DNA sequencing, or PCR-high resolution melting curve analysis. ResultsFour SNPs (rs13381619, rs9955626, rs1792658, and rs1792671) within SMAD2, one SNP within SMAD3 (rs41473580), two SNPs within SMAD4 (rs7229678 and rs9304407), and one SNP within SMAD7 (rs12956924) were significantly associated with susceptibility only to UC. rs13381619 within SMAD2, rs4147358 within SMAD3, rs9304407 within SMAD4, and rs12956924 within SMAD7 exhibited the strongest association (p < 0.001, p = 0.021, p = 0.005, and p = 0.001, respectively). Furthermore, rs4147358 of SMAD3 altered the expression of a luciferase reporter gene in Jurkat T cell line in vitro. ConclusionsGenetic variants of several SMAD family of genes might alter the balance of differentiation between Th17 and Treg, resulting in the development of IBD, especially UC.

Progress of research on toll-like receptors family gene polymorphism and susceptibility to tuberculosis

Tuberculosis is a chronic infectious disease caused by Mycobacterium (M.) tuberculosis. Innate immunity plays an important role in the response to M. tuberculosis. Toll-like receptors (TLRs) are important pattern recognition receptors in innate immunity. TLRs serve as switches that play decisive roles in identifying pathogens-related components. Previous studies found that TLR1, TLR2, TLR4, TLR9 were essential to promote the development of innate immune responses. The SNPs of rs4833095, rs5743618, rs3923647 of TLR1, rs57473708, rs3804099 of TLR2 and rs352139, rs5743836 of TLR9 were closely related to the susceptibility of tuberculosis in some populations. And there appeared certain relationship between the polymorphisms of TLR3, TLR6, TLR7, TLR8, TLR10 and the susceptibility of tuberculosis. The normal function of TLRs ensures the body's normal immune response to M. tuberculosis. The diversity of TLRs genes allows different individuals to respond differently to the same pathogen. Studies targeting on the relationship between single nucleotide polymorphism in TLRs and susceptibility to tuberculosis can predict the susceptibility to tuberculosis in some populations, as well as discover new drugs targets.

Association of farm-related factors with characteristics profiles of extended-spectrum β-lactamase- / plasmid-mediated AmpC β-lactamase-producing Escherichia coli isolates from German livestock farms

Resistance to β-lactam antibiotics, including third-generation cephalosporins, is of major concern for animal and human health. In this study, extended-spectrum β-lactamase (ESBL) / plasmid-mediated AmpC (pAmpC) β-lactamase -producing Escherichia coli isolates from German livestock farms were characterised and associations of these isolate characteristics with farm-related factors were investigated across different types of livestock.A total of 469 isolates originating from 150 farms (34 broiler farms, 38 fattening pig farms, 43 dairy cattle farms, 35 beef cattle farms) was included in the analyses. ESBL-gene family, phylogroup and phenotypic antimicrobial susceptibility for several antimicrobial agents were determined. This data was used to define different profiles characterising the isolates. Multivariate analyses using a distance-based non-parametric approach were performed to investigate associations between the profiles of the isolates and farm-related factors (e.g. management, husbandry, and environment of the farms).Co-occurrence of ESBL-gene families were not found in any of the isolates analysed. Sixty-eight percent of the isolates carried blaCTX-M variant genes. The frequency of phylogroups was as follows: A (55%), B1 (35%), D (17%) and B2 (3%). The most frequent phenotypic non-wildtype profile was non-wildtype status of solely cefepime (27%). Profiles of isolates from broilers differed substantially from those of other isolates. Associations between farm-related factors and characteristics profiles differed, depending on the isolate characteristics included in the analyses. Some factors describing the farm environment, like waterfowl in the surrounding of the farm, were associated with all tested profiles.The epidemiological method applied defines distances between isolates on basis of isolate characteristics data and is capable of analysing associations between isolate characteristics and epidemiological factors. As additional data, such as plasmid characteristics, gene type, or sequence information could be included in future studies, the method is suitable to identify points of action to reduce the occurrence of antimicrobial resistant bacteria.

Graves' disease in children in the two decades following implementation of an iodine prophylaxis programme.

Grave’s disease (GD) is a form of thyroid autoimmune disease characterised by hyperthyroidism. It is a rare clinical problem in paediatrics. Development of disease is the result of genetic susceptibility and some environmental factors. One of the best-documented environmental factors involved in thyroid autoimmunity is iodine excess. The aim of our study was to analyse the clinical course and response to pharmacological treatment in children diagnosed with Graves’ disease in first two decades after mandatory salt iodination. Records of 94 children diagnosed with GD in the years 1998-2017 were analysed. Medical data of patients was compared between two decades following implementation of iodine prophylaxis: 1998-2007 (first-decade group – FDG) and 2008-2017 (second-decade group – SDG); 34 and 60 patients, respectively. Medical data of FDG was obtained from archival records and previous analysis performed in 2006. Data of 60 patients from SDG were obtained from currently available medical records. Results were statistically analysed using Microsoft Excel and Statistica 11 software. Results: In our study, after mandatory salt iodination, the tendency of an increase in newly diagnosed GD in children without family susceptibility was observed. The antibody profile indicates the significant contribution of the autoimmune process involving all thyroid antigens; therefore, the term “autoimmune hyperthyroidism” seems to be more appropriate than classical GD in this group of patients. The first-choice treatment with methimazole rarely causes adverse events during the therapy, and they have benign character.

The study on the association between Beijing genotype family and drug susceptibility phenotypes of Mycobacterium tuberculosis in Beijing

The predominant prevalent Mycobacterium tuberculosis (M. tb) lineage was the Beijing genotype family in Beijing. There has been no systematic study on the association between drug resistance and Beijing genotype. Here we collected 268 M. tb strains, analyzed the background information and the bacteriological characteristics. The mean age of the cases was 40.12 years; male patients were almost three times than female patients. After genotyping analyzation, 81.7% (219/268) strains were categorized as Beijing genotype; no significant difference was observed between Beijing and non-Beijing genotype in gender, age and treatment history. Drug susceptibility testing (DST) analyzation demonstrated that 172 (64.2%) strains were fully sensitive to all drugs (Isoniazid, Rifampin, Streptomycin, and Ethambutol), while 96 (35.8%) strains were resistant to at least one of the drugs. Beijing genotype strains exhibited a significantly higher clustering rate. However, no significant association relationship was observed between drug resistance and Beijing genotype family. The study provided insights into the genotype diversity and revealed that the frequencies of drug-resistance of Beijing genotype strains.It would be helpful for the establishment of the efficient tuberculosis (TB) prevention and control strategy in Beijing.

The joint effects of family risk of obesity and neighborhood environment on obesity among women

Obesity is a significant health problem in the United States that has encouraged a search for modifiable risk factors, such as walkable neighborhood designs. Prior research has shown linkages between a family history of obesity (i.e., due to either genetic or non-genetic factors) and an individual's risk of elevated body mass index (BMI). Yet, we know little about the possible interactions between neighborhood walkability and family susceptibility to unhealthy BMI in predicting individual BMI. This paper addresses this important research gap using a sample of 9918 women, derived from vital and administrative data in the Utah Population Database. We use a novel indicator of familial risk (a summary measure of siblings' BMI) and a neighborhood walkability score to capture familial susceptibility and environmental exposures, respectively. The analysis focuses on distinct risk combinations of familial susceptibility and neighborhood walkability. Compared with the “best” combination of lean family BMI history and more walkable neighborhoods, women in all of the other three family weight history/neighborhood categories show greater risks of obesity. Our results also indicate that the neighborhood environment has a strong association with individual obesity among women with higher family risk of obesity but that the association between neighborhood environment and individual obesity is even stronger for women with a lower family risk of obesity.

Meta-analysis of the correlation between the rs17401966 polymorphism in kinesin family member 1B and susceptibility to hepatitis B virus related hepatocellular carcinoma.

Background/AimsThe association between the kinesin family member 1B (KIF1B) gene polymorphism and the risk of hepatitis B virus-related hepatocellular carcinoma (HCC) has been investigated in many peer-reviewed studies. However, scholars have failed to replicate these results in validation tests. The purpose of the present study was to explore whether the KIF1B rs17401966 polymorphism was associated with susceptibility to HCC.MethodsThe results of case-controlled studies on the correlation between the KIF1B rs17401966 polymorphism and HCC susceptibility were collected using Google Scholar and the EMBASE, PubMed and CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total of 12 cohorts were included in this study.ResultsThe 12 cohorts were integrated, and the results showed that the rs17401966 polymorphism reduced the risk for HCC under the allele, heterozygous, homozygous, and dominant models but not under the additive or recessive models. Moreover, the merged results showed strong heterogeneity, and the cumulative meta-analysis results were unreliable. A genetic differentiation analysis of the 12 cohorts found different degrees of genetic differentiation between the 5 cohorts in Zhang et al.’s study and the cohorts in the other studies. We further divided the 12 study cohorts into 2 subgroups based on fixation index value; however, the results of that analysis were inconsistent.ConclusionsThe results of this meta-analysis were not able to verify the association between the KIF1B rs1740199 polymorphism and HCC risk. Therefore, a well-designed, large-scale, multicenter validation study is needed to confirm the relationship.

Abstract 19428: Evaluating the Risk of Rheumatic Heart Disease Among Family Members of Children Identified With Latent RHD in School-based Echocardiographic Screening

Background: Poorly understood genetic susceptibility factors influence who develops acute rheumatic fever (ARF) and who develops the long-term complication, rheumatic heart disease (RHD). Risk of RHD in family members - and thus the need for screening of first degree relatives - once an index case has been identified, is not known. Methods: Sixty RHD positive children (30 borderline 30 definite RHD) and 67 age &amp; gender matched controls were recruited from previous school-based echocardiographic screening. All first-degree relatives ≥ 5 years were invited for echocardiographic screening (2012 World Heart Federation Criteria). Absent family members were recorded with reason for absence including death. Continuous variables were compared using 2-tailed independent samples t-test, categorical variables by Fisher’s Exact Test, and relative risk was used to compare cases and controls. Results: A total of 454/733 (62%) family members were screened (106 mothers, 48 fathers &amp; 300 siblings). Definite RHD was more common in childhood siblings of cases than controls (p=0.05), and children with RHD were 4.5 times as likely to have a sibling with RHD compared to controls. Mothers had more RHD than fathers without regard to child’s screening status. Conclusions: Siblings of children identified with latent RHD are at greater risk of having RHD and screening of these children should be considered. While no adult RHD screening data exists from sub-Saharan Africa, this study suggests that the prevalence of occult RHD in adult women is quite high (9.4%). Genotyping studies are needed to fully understand individual and family susceptibility to RHD.

Frequent nocturnal awakening in children: prevalence, risk factors, and associations with subjective sleep perception and daytime sleepiness.

BackgroundNocturnal awakening is the most frequent insomnia complaint in the general population. In contrast to a growing knowledge based on adults, little is known about its prevalence, correlated factors, and associations with subjective sleep perception and daytime sleepiness in children. This study was designed to assess the prevalence and the correlate factors of frequent nocturnal awakening (FNA) among Chinese school-aged children. Furthermore, the associations of FNA with subjective sleep perception and daytime sleepiness were examined.MethodsA random sample of 20,505 children aged 5.00 to 11.92 years old (boys: 49.5% vs. girls: 50.5%) participated in a cross-sectional survey, which was conducted in eight cities of China. Parent-administered questionnaires were used to collect information on children’s sleep behaviors, sleep perception, and potential influential factors of FNA from six domains. Univariate and multivariate logistic regression models were performed.ResultsThe prevalence of FNA was 9.8% (10.0% for boys vs. 8.9% for girls) in our sampled children. The prominent FNA-related factors inclued biological health problems, such as overweight/obesity (OR = 1.70), chronic pain during night (OR = 2.47), and chronic respiratory condition (OR = 1.23), poor psychosocial condition, such as poor mental and emotional functioning (OR = 1.34), poor sleep hygiene, such as frequently doing exciting activities before bedtime (OR = 1.24) and bedtime resistance (OR = 1.42), and parents’ history of insomnia (OR = 1.31). FNA was associated with subjective poor sleep quality (OR = 1.24), subjective insufficient sleep (OR = 1.21), and daytime sleepiness (OR = 1.35).ConclusionFNA was associated with poor sleep and daytime sleepiness. Compared to sleep environment and family susceptibility, chronic health problems, poor psychosocial condition, and poor sleep hygiene had greater impact on FNA, indicating childhood FNA could be partly prevented by health promotion, by psychological intervention, and by improving sleep hygiene routine.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-244X-14-204) contains supplementary material, which is available to authorized users.

Genetic Polymorphism of Matrix Metalloproteinase Family and Chronic Obstructive Pulmonary Disease Susceptibility: a Meta-analysis

Matrix metalloproteinase (MMP) family is considered to be associated with chronic obstructive pulmonary disease (COPD) pathogenesis, however, no consistent results have been provided by previous studies. In this report, we performed Meta analysis to investigate the association between four kinds of MMP single nucleotide polymorphisms (SNP, MMP1 -1607 1G/2G, MMP3 -1171 5A/6A, MMP9 -1562 C/T, MMP12 -82 A/G) and COPD risk from 21 studies including 4184 cases and 5716 controls. Both overall and subgroup association between SNP and COPD susceptibility were tested. There was no evident association between MMP polymorphisms and COPD susceptibility in general population. On the other hand, subgroup analysis suggested that MMP9 -1562 C/T polymorphism was related to COPD, as we found that C allele carriers were at lower risk in some subgroups stratified by lung function, age and genotype identification method, compared with TT homozygotes. Our results indicated the genotype TT might be one genetic risk factor of severe COPD.

Drug-reaction eosinophilia and systemic symptoms and drug-induced hypersensitivity syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a rare, severe cutaneous adverse reaction characterised by fever, rash, lymphadenopathy, eosinophilia and/or other leukocyte abnormalities, and internal organ involvement and often has a relapsing-remitting course despite withdrawal of the drug. The drugs that are most implicated include aromatic anticonvulsants, allopurinol, sulphonamides, antiretrovirals (abacavir and nevirapine), and minocycline. The pathogenesis of DRESS/DIHS is far from clear but probably involves a combination of impaired pharmacokinetics and the accumulation of drug metabolites, the sequential reactivation of the herpesvirus family and genetic susceptibility conferred by the association with certain human leukocyte antigen (HLA) class I alleles. The strong association between abacavir and HLA-B*5701 has enabled pharmacogenetics screening to be employed successfully to minimise the occurrence of hypersensitivity. A prolonged course of oral corticosteroids is required to treat DRESS/DIHS, given the relapsing-remitting nature of the condition with i.v. immunoglobulin and valgangciclovir reserved for refractory or life-threatening cases.

Genetic polymorphism of MMP family and coronary disease susceptibility: A meta-analysis

The issue that genetic polymorphism of matrix metalloproteinase (MMP) family is in association with coronary disease is controversial. So we did a meta-analysis to clarify it clearly. We made a literature search of PubMed, the Web of Science, and Cochrane Collaboration's database to identify eligible reports. The methodological quality of each included studies was assessed. We calculated the pooled ORs with their 95%CI for each genetic polymorphism in STATA 11 software. Separate analysis was performed to address the consistency of results across the subgroup with different continents. A total of 39 studies were included, with a sample of 42269 individuals. This meta-analysis provided evidence that genetic polymorphism of MMP1-1607 1G/2G, MMP3-Gly45lys, MMP3-376 G/C, MMP3-1171 5A/6A, MMP9-1562 C/T and MMP9-R279Q have a small to medium effect on incidence of coronary disease. There was no evidence that MMP1-519 A/G, MMP1-340 T/C and MMP2-1306 C/T polymorphism could increase risk of coronary disease. Results from subgroup analysis supported a relation between MMP3-1711 5A allele, MMP9-1562 C allele and coronary disease especially in Asian population. The results provide moderate association between the six common genetic polymorphism of matrix metalloproteinase family and coronary disease. However, the challenge for researcher is identifying separate effect on different races.

Birth defects in newborns and stillborns: an example of the Brazilian reality.

BackgroundThis study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects.MethodsFor all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases.ResultThe incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death.ConclusionsThe current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments.