N-acetyltransferase 2 (NAT2) gene polymorphisms in colon and lung cancer patients

Background  

N-acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines moeities found in many therapeutic drugs, chemicals and carcinogens. The gene encoding NAT2 is polymorphic, thus resulting in rapid or slow acetylator phenotypes. The acetylator status may, therefore, predispose drug-induced toxicities and cancer risks, such as bladder, colon and lung cancer. Indeed, some studies demonstrate a positive association between NAT2 rapid acetylator phenotype and colon cancer, but results are inconsistent. The role of NAT2 acetylation status in lung cancer is likewise unclear, in which both the rapid and slow acetylator genotypes have been associated with disease.     

Frequency of single nucleotide polymorphisms in NOD1 gene of ulcerative colitis patients: a case-control study in the Indian population

Background  

Epidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease. However, a very similar gene encoding Nod1 protein still has not been well documented for its association with Ulcerative colitis patients. Detection of polymorphism in NOD1 gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain (NBD) of NOD1 gene in context to Indian population.     

N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease

Background  

Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is unknown, but genetic predisposition and environmental factors may cause the disease. Sequence variations in N-acetyltransferase 2 (NAT2) gene leading to slow acetylation process have been associated with PD, but results are contradictory.     

<Emphasis Type="Italic">N-acetyltransferase 8</Emphasis>, a positional candidate for blood pressure and renal regulation: resequencing,association and <Emphasis Type="Italic">in silico</Emphasis> study

Background  

Kidneys have an important function in blood pressure (BP) regulation and elevated BP may lead to kidney failure. Chr2p12-p13 region linked to BP traits in multiple studies harbours a potential candidate for BP and renal function, N-acetyltransferase 8 (NAT8) expressed in embryonic and adult kidney and associated with nephrotoxicity response.     

The association between genetic variants in <Emphasis Type="Italic">hMLH1</Emphasis> and <Emphasis Type="Italic">hMSH2</Emphasis> and the development of sporadic colorectal cancer in the Danish population

Background  

Mutations in the mismatch repair genes hMLH1 and hMSH2 predispose to hereditary non-polyposis colorectal cancer (HNPCC). Genetic screening of more than 350 Danish patients with colorectal cancer (CRC) has led to the identification of several new genetic variants (e.g. missense, silent and non-coding) in hMLH1 and hMSH2. The aim of the present study was to investigate the frequency of these variants in hMLH1 and hMSH2 in Danish patients with sporadic colorectal cancer and in the healthy background population. The purpose was to reveal if any of the common variants lead to increased susceptibility to colorectal cancer.     

Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a Tunisian population

Cigarette smoking is the predominant risk factor for bladder cancer in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and GSTT1 null genotypes in bladder cancer development in North Tunisia. In all groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30–51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1–323.76).     

Foxp3<Superscript>+</Superscript> Regulatory T Cells,Th17 Effector Cells,and Cytokine Environment in Inflammatory Bowel Disease

Background  

Inflammatory bowel disease (IBD) is thought to result from an aberrant immune response. Inflammation in IBD may be caused by the loss of homeostasis between CD4⁺ CD25^high Foxp3⁺ regulatory cells (T _reg) and proinflammatory Th17 cells. The aim of this study was to investigate T _reg and Th17 cells in the peripheral blood and intestinal mucosa of IBD patients and to assess the mucosal cytokine environment.     

PALB2 variants in hereditary and unselected Finnish Prostate cancer cases

Background  

PALB2 1592delT mutation is associated with increased breast cancer and suggestive prostate cancer (PRCA) risk in Finland. In this study we wanted to assess if any other PALB2 variants associate to increased PRCA risk and clinically describe patients with formerly found PALB2 1592delT mutation.     

Rectal gel application of <Emphasis Type="Italic">Withania somnifera</Emphasis> root extract expounds anti-inflammatory and muco-restorative activity in TNBS-induced Inflammatory Bowel Disease

Background  

Inflammatory Bowel Disease (IBD) is marked with chronic inflammation of intestinal epithelium driven by oxidative stress. Traditional treatments with plant extracts gained renewed interest due to their ability to ameliorate the multi factorial conditions like inflammation. We investigated the beneficial effects of Withania somnifera in Trinitro Benzyl Sulfonic Acid (TNBS) induced experimental IBD through a rectally applicable formulation.     

Evaluation of <Emphasis Type="Italic">SLC11A1</Emphasis>as an inflammatory bowel disease candidate gene

Background  

Significant evidence suggests that a promoter polymorphism withinthe gene SLC11A1 is involved in susceptibility to both autoimmune and infectious disorders. The aim of this study was to evaluate whether SLC11A1 has a role in the susceptibility to inflammatory bowel disease (IBD) by characterizing a promoter polymorphism within the gene and two short tandem repeat (STR) markers in genetic proximity to SLC11A1.     

Founder mutations in <Emphasis Type="Italic">BRCA1/2</Emphasis> are not frequent in Canadian Ashkenazi Jewish men with prostate cancer

Background  

Relatives of BRCA1 and BRCA2 mutation carriers have long been proposed by epidemiological studies to have an increased risk of developing prostate cancer. In the Ashkenazi Jewish (AJ) population, the existence of 3 frequent founder mutations, 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 greatly facilitates screening for carriers.     

Immune checkpoint molecules soluble program death ligand 1 and galectin‐9 are increased in pregnancy

Problem

Pregnancy requires balance between tolerance to the haploidentical fetus and the mother's ability to mount immune responses. There are parallels to this phenomenon that occur in metastatic cancer. We assessed soluble program death ligand‐1 soluble PD‐L1 (sPD‐L1) and galectin‐9 in the blood of pregnant women during gestation as these molecules are highly involved in immune suppression during cancer.

Method of study

Maternal blood was collected from 30 primigravida women at monthly intervals during pregnancy, delivery and 6‐week post‐partum. Blood was analyzed for sPD‐L1 and galectin‐9 concentrations by ELISA. Term placentas were collected in formalin and IHC was completed for PD‐L1 and galectin‐9 expression.

Results

Maternal blood levels of sPD‐L1 (0.438 ng/mL) and galectin‐9 (1976 pg/mL) were elevated early in normal pregnancies compared to non‐pregnant controls (0.242 ng/mL and 773 pg/mL, respectively). sPD‐L1 increased throughout gestation, whereas galectin‐9 remained elevated until parturition; both proteins returned to control levels post‐partum. Women carrying male fetuses had significantly higher galectin‐9 levels, but not sPD‐L1, than those carrying females (2263 pg/mL vs 1874 pg/mL; P = .0005). Trophoblast cells of the term placenta coexpress galectin‐9 and PD‐L1.

Conclusion

Immune‐regulatory molecules galectin‐9 and sPD‐L1 increased during pregnancy and may play a role in immune tolerance that is critical for the fetus.     

Habit formation in context: Context-specific and context-free measures for tracking fruit consumption habit formation and behaviour

Objectives

Interventions promoting habitual fruit consumption have the potential to bring about long-term behaviour change. Assessing the effectiveness of such interventions requires adequate habit and behaviour measures. Habits are based on learned context-behaviour associations, so measures that incorporate context should be more sensitive to expected habit and behaviour changes than context-free measures. This study compared context-specific and context-free measures of fruit consumption habit and behaviour following a 3-week habit formation intervention.

Design

Prospective online study (n = 58).

Methods

Behaviour frequency was assessed across five timepoints, retrospectively (Time 1 [T1], T5) or via daily diary data (uploaded weekly at T2, T3 and T4). Habit strength was assessed before (T1) and immediately after the intervention (T4), and again 2 weeks later (T5). Analyses of variance were run, with time and context specificity as within-subject factors, and habit and behaviour frequency as dependent measures.

Results

An interaction between time and context specificity was found in both analyses (habit: F(2,114) = 12.848, p < .001, part.η² = .184; behaviour: F(2,114) = 6.714, p = .002, part.η² = .105). Expected habit formation patterns 5 weeks post-baseline were only detected by the context-specific habit measure. Likewise, increased behaviour frequency was only found when the target context was specified (p's < .001).

Conclusions

Assessments of purposeful dietary habit and behaviour change attempts should incorporate context-specific measurement.     

Use of complementary and alternative medicine in Germany – a survey of patients with inflammatory bowel disease

Background  

Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). The aim of our study was to evaluate the use of CAM in German patients with IBD.     

The effects of social interactions on momentary stress and mood during COVID-19 lockdowns

Objective

Social interactions are vital for our well-being, particularly during times of stress. However, previous studies linking social interactions to psychological outcomes during the COVID-19 pandemic have largely been retrospective and/or cross-sectional. Thus, we tested four preregistered hypotheses (H1–H4) concerning the real-time effect of social interactions on momentary changes in stress and mood during two COVID-19 lockdowns.

Design

We used an ecological momentary assessment approach in 732 participants in spring 2020 (burst 1) and in a subsample of these participants (n = 281) during a further lockdown in autumn/winter 2020 (burst 2).

Methods

Participants reported their stress and mood in a smartphone app five times per day for 7 days and indicated the nature and frequency of their recent social interactions.

Results

Social interactions (H1) and their frequency (H2) improved momentary affect (e.g., social interactions increased mood valence: estimate = 2.605, p < .001 for burst 1). This was particularly the case for face-to-face interactions which, compared with other types of interactions, reduced momentary stress (e.g., estimate = −2.285, p < .001 for burst 1) and boosted mood (e.g., estimate = 1.759, p < .001 for burst 1) across both lockdowns, even when controlling for the pleasantness of the interaction and the closeness of the interaction partner (H3). We also show that individual differences in people's responsiveness to different social rewards modulated the impact of social interactions on momentary mood (H4).

Conclusions

This study extends findings from cross-sectional and retrospective studies by highlighting the real-time affective benefits of social interactions during COVID-19 lockdown. The results have important implications for the (self-) management of stress and mood during psychologically demanding periods.     

Antibody dynamics to SARS-CoV-2 in asymptomatic COVID-19 infections

Background

The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.

Measure

Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.

Results

A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.

Conclusion

Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies.

     

The occurrence of germline <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis>sequence alterations in Slovenian population

Background  

The BRCA1 and BRCA2 mutation spectrum and mutation detection rates according to different family histories were investigated in 521 subjects from 322 unrelated Slovenian cancer families with breast and/or ovarian cancer.     

Clinical predictors of inflammatory bowel disease in a genetically well-defined Caucasian population

Background  

Crohn's disease (CD) and ulcerative colitis (UC), the two main types of inflammatory bowel disease (IBD), are multifactorial conditions of unknown etiology. The objective of this study is to examine the combined gene-environment interactions influencing IBD susceptibility in a well-defined Caucasian cohort in rural mid-America.     

Parent and self-report of sleep-problems and daytime tiredness among adolescents with inflammatory bowel disease and their population-based controls

Study Objectives:

To evaluate the frequency of sleep problems and daytime tiredness among adolescents with inflammatory bowel disease (IBD) in comparison with their healthy peers.

Design:

Parent and self-reports of sleep problems and daytime tiredness.

Setting:

Questionnaire-based postal survey.

Intervention:

N/A.

Participants:

One hundred sixty Finnish adolescents with IBD; 236 adolescents matched for age, sex, and place of residence; and the parents of both groups.

Measurements and Results:

Sleep Self-Report and sleep questions of the Child Behavior Check-List, and Youth Self-Report. The parents of adolescents with IBD reported in their index child more trouble sleeping (P < 0.01), more nightmares (P < 0.01), sleeping more than most children during the day/night (P < 0.001), and overtiredness (P < 0.001) than did the parents of control subjects. In contrast, adolescents with IBD themselves did not report more problems than their peers. However, in the group of patients with self-reported severe IBD symptoms, both the parents and the adolescents reported trouble sleeping and overtiredness more often (P values < 0.01) than in the group with mild symptoms or control subjects. Adolescents with severe IBD reported more often that their symptoms affected the quality of their sleep (P < 0.001) than did adolescents with mild disease.

Conclusions:

Adolescents with severe IBD symptoms have disturbed sleep and are overtired more often than are adolescents with mild IBD symptoms or control subjects. Thus, in adolescents with severe IBD symptoms, evaluating sleep is important in characterizing the disease burden. Both parent and adolescent reports are needed for comprehensive assessment of sleep in the young.

Citation:

Pirinen T; Kolho KL; Simola P; Ashorn M; Aronen ET. Parent and self-report of sleep-problems and daytime tiredness among adolescents with inflammatory bowel disease and their population-based controls. SLEEP 2010;33(11):1487-1493.     

NAT2 gene polymorphisms in three indigenous groups in the Colombian Caribbean Coast region

Objective:

To study the NAT2 gene polymorphisms 481T, 590A and 857A in the Chimila, Wiwa and Wayuu indigenous groups of the Colombian Caribbean to determine the frequencies of the alleles NAT2*4, NAT2*5, NAT2*6, and NAT2*7 and to determine the types of acetylators present in these populations.

Methods:

A total of 202 subjects were studied: 47 Chimila, 55 Wiwa, and 100 Wayuu. The polymorphisms were identified using a real-time PCR method for allelic discrimination designed using Taqman of Applied Biosystems.

Results:

The following alleles were found at the highest frequency in the following groups: the NAT2*4 allele (wild type) in the Wayuu group (55.3%), the NAT2*5 allele in the Wiwa group (34.5%), and the NAT2*7 allele in the Chimila group (24.2%). A higher frequency of the rapid acetylator status was found in the Wayuu group (31.3%) and Chimila group (29.5%) compared with the Wiwa group (12.7%). The intermediate acetylator status distribution was very similar in all three groups, and the frequency of the slow acetylator status was higher in the Wiwa group (32.7%) compared with the Chimila and Wayuu groups (20.5% and 21.2%, respectively).

Conclusion:

The results demonstrated the allelic distribution and pharmacogenetic differences of the three groups studied and revealed the most frequent acetylator status and phenotype. Because of the high prevalence of slow acetylators, a greater incidence of tuberculosis (TB) drug-induced hepatotoxicity is predicted in these populations, with a higher frequency in the Wiwa group.