To investigate the link between extreme diurnal preference, delayed sleep phase syndrome, and a length polymorphism in Per3.
Subjects were genotyped using polymerase chain reaction.
Subjects with ...defined diurnal preference as determined by the Horne-Ostberg questionnaire and patients with delayed sleep phase syndrome.
The Per3 polymorphism correlated significantly with extreme diurnal preference, the longer allele associating with morningness and the shorter allele with eveningness. The shorter allele was strongly associated with the delayed sleep phase syndrome patients, 75% of whom were homozygous.
The length of the Per3 repeat region identifies a potential genetic marker for extreme diurnal preference.
Sarcoidosis Baughman, Robert P; Lower, Elyse E; du Bois, Roland M
The Lancet (British edition),
03/2003, Letnik:
361, Številka:
9363
Journal Article
Recenzirano
There have been several new insights into the cause and treatment of sarcoidosis. Studies of genetic variation have shown that specific genetic polymorphisms are associated with increased risk of ...disease or affect disease presentation. These polymorphisms include variation of MHC and cytokines such as tumour necrosis factor (TNF). Not all investigators have come to the same conclusion, suggesting an interaction of various factors, including the patient's ethnic origin. Treatment of sarcoidosis varies considerably. Patients with symptomatic disease for more than 2–5 years have been of particular interest. Corticosteroids remain the standard of care in such cases, but immunosuppressive drugs have proved steroid-sparing in many patients. New agents, including pentoxifylline, thalidomide, and infliximab have proved useful in selected cases. The effectiveness of these agents seems to lie in their ability to block TNF, especially in the treatment of chronic disease.
Recent studies suggest that there might be an association between albuterol use and worsening asthma in patients homozygous for arginine (Arg/Arg) at codon 16 of the β-receptor. However, it is not ...known whether similar responses occur in Arg/Arg patients receiving long-acting β
2-agonists.
We sought to evaluate the effects of variation in the β
2-adrenergic receptor gene
(ADRB2) on clinical response to salmeterol administered with fluticasone propionate.
Subjects (n = 183) currently receiving short-acting β
2-agonists were randomized to twice-daily therapy with salmeterol, 50 μg, administered with fluticasone propionate, 100 μg, in a single inhaler or daily therapy with montelukast for 12 weeks, followed by a 2- to 4-day run-out period.
There was sustained and significant improvement (
P < .001) over baseline in all measures of asthma control in subjects receiving salmeterol, regardless of Arg16Gly genotype. Morning peak expiratory flow in subjects with the Arg/Arg genotype showed 89.0 ± 16.1 L/min improvement over baseline compared with 93.7 ± 12.7 L/min for Gly/Gly subjects and 92.5 ± 11.9 L/min for Arg/Gly subjects. Pairwise changes were similar for Arg/Arg compared with Gly/Gly or Arg/Gly genotypes (estimated differences, 4.7 L/min and 3.5 L/min, respectively). Responses did not appear to be modified by haplotype pairs. During the run-out period, all subjects had predictable and similar decreases in measures of asthma control, with no differences between genotypes.
Response to salmeterol does not vary between
ADRB2 genotypes after chronic dosing with an inhaled corticosteroid.
Analyses from this study indicate that genetic polymorphisms leading to Arg16Gly sequence changes within the β
2-adrenergic receptor do not affect patients' responses to recommended asthma therapy with salmeterol and fluticasone propionate.
In January 2009, the National Heart, Lung, and Blood Institute convened a 28-member multidisciplinary Working Group to update the recommendations of a 2004 National Heart, Lung, and Blood Institute ...Working Group focused on Guidelines to the Return of Genetic Research Results. Changes in the genetic and societal landscape over the intervening 5 years raise multiple questions and challenges. The group noted the complex issues arising from the fact that technological and bioinformatic progress has made it possible to obtain considerable information on individuals that would not have been possible a decade ago. Although unable to reach consensus on a number of issues, the working group produced 5 recommendations. The working group offers 2 recommendations addressing the criteria necessary to determine when genetic results should and may be returned to study participants, respectively. In addition, it suggests that a time limit be established to limit the duration of obligation of investigators to return genetic research results. The group recommends the creation of a central body, or bodies, to provide guidance on when genetic research results are associated with sufficient risk and have established clinical utility to justify their return to study participants. The final recommendation urges investigators to engage the broader community when dealing with identifiable communities to advise them on the return of aggregate and individual research results. Creation of an entity charged to provide guidance to institutional review boards, investigators, research institutions, and research sponsors would provide rigorous review of available data, promote standardization of study policies regarding return of genetic research results, and enable investigators and study participants to clarify and share expectations for the handling of this increasingly valuable information with appropriate respect for the rights and needs of participants.
This study aimed to investigate the association between brain-derived neurotrophic factor (
) and cyclic adenosine monophosphate response element binding protein (
) gene polymorphisms and ...schizophrenia.
This study used a case-control design, and diagnoses were made based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. One hundred and thirty-four patients with schizophrenia were recruited from the Third People's Hospital of Zhongshan City from January 2018 to April 2020. Sixty-four healthy controls were recruited from the same region. Genotypes at the
gene single nucleotide polymorphisms rs11030101, rs2030324, and rs6265 and the
gene single nucleotide polymorphisms rs6740584 and rs2551640 were determined using a MassARRAY mass spectrometer. Linkage disequilibrium and haplotype analyses were performed, and genotype and allele frequencies were compared between groups. The positive and negative symptom scale (PANSS) was used to evaluate the association between the
and
gene polymorphisms and schizophrenic symptoms.
There was no significant difference in genotype or allele frequencies for rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 between schizophrenic patients and controls (p > 0.05). In addition, there were no significant differences in rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 genotype frequencies between the two groups in the dominant, recessive, or over-dominant models (p > 0.05). Three loci in the BDNF gene and two loci in the CREB gene were in a state of strong linkage disequilibrium. The frequency of haplotype AAC (rs11030101/rs2030324/rs626), composed of three loci in the BDNF gene, was significantly increased in schizophrenic patients compared with control subjects. There were significant differences in the subscores of PANSSS for negative symptoms, in patients with different rs11030101 genotypes of the
gene (
< 0.05). There was also significant differences in the PANSS scores for the general symptom G12 (judgment and lack of insight) in patients with different rs6265 genotypes of the
gene (
< 0.05).
The
gene rs11030101/rs2030324/rs6265 AAC haplotype was potentially associated with an increased risk of schizophrenia. In addition, genotypes at the rs11030101 and rs6265 loci may affect the negative symptoms and general symptoms of schizophrenic patients, respectively.
Several studies suggest an important role of Interleukin-27 in the development of atherosclerosis. The aim of this study was to establish whether the
gene polymorphisms are associated with premature ...coronary artery disease and/or other cardiovascular risk factors. Four
gene polymorphisms were selected and genotyped in 1162 premature coronary artery disease cases and 1107 controls. rs26528
and rs40837
alleles were significantly associated with a lower risk of premature coronary artery disease under different inheritance models (P
= 0.046; P
= 0.002; P
= 0.007 for rs26528T; P
= 0.008 and P
= 0.031 for rs40837). The rs40837
allele was also associated with a lower risk of insulin resistance, in cases (P
= 0.037) and controls (P
= 0.008; P
= 0.047; P
= 0.014; P
= 0.006), while the rs26528
allele was associated with a lower risk of insulin resistance only in the control group (P
= 0.016; P
= 0.021). Interleukin-27 plasma levels were measured in 450 controls and 450 cases, and were significantly higher in cases compared to controls (P = 0.004). However, Interleukin-27 plasma levels were not associated with
polymorphisms. Luciferase assays showed that co-transfection of the rs40837
allele and miR-379-5p significantly decreased luciferase gene expression. Our study shows for the first time, that IL
gene polymorphisms are associated with premature coronary artery disease and with some metabolic parameters. The rs40837
allele in presence of miR-379-5p significantly decreased luciferase gene expression.
It has been found that the -2518 C-C motif ligand (CCL)-2 promoter variant increases the risk of developing active tuberculosis (TB).
To study the association between -2518 variants and ...susceptibility to TB.
We searched Medline, PubMed and the Wan Fang databases for human genetic studies on whether the -2518 CCL2 polymorphism influences the expression of active TB. Articles published from January 1998 to November 2010 were included. A random effects model was conducted in the meta-analysis.
The CCL2-2518G allele (OR 1.51, 95%CI 1.11-2.04, P = 0.008) showed significant association with susceptibility to TB. In genotype analysis, the recessive model (CCL2 genotype GG, OR 1.66, 95%CI 1.19-2.33, P = 0.003) was slightly superior to the dominant model (G carrier genotypes OR 1.53, 95%CI 1.07-2.17, P = 0.018). These observations were prominent among Asians and Latin-Americans of Hispanic ancestry, but not in Africans from Ghana and South Africa. The presence of epistatic genes in one population but not in the other, environmental differences and pathogen virulence may account for this.
The CCL2-2518G allele increases the risk of developing TB in Asians and Hispanics.
A meta-analytical review of 20 studies (n = 3907) of the association between DRD4 polymorphism and novelty seeking suggests the following conclusions: (a) on average, there is no association between ...DRD4 polymorphism and novelty seeking (average d = 0.06 with 95% CI of +/- 0.09), where 13 reports suggest that the presence of longer alleles is associated with higher novelty seeking scores and seven reports suggest the opposite; (b) there is a true heterogeneity among the studies (ie, unknown moderators do exist) but the strength of the association between DRD4 polymorphism and novelty seeking in the presence of any (unknown) moderator is likely to be weak; (c) search for moderators has not yielded any reliable explanation for the variability among studies. We propose that to find such moderators, theory-driven research for potential interaction, coupled with larger sample sizes should be employed. The growing availability of powerful statistical techniques, high-throughput genotyping and large numbers of polymorphic markers such as single nucleotide polymorphisms makes such proposed studies increasingly feasible.
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