Association between TLR1 polymorphisms and alopecia areata

Abstract

Toll-like receptors (TLRs) may contribute to the process of autoimmune attacks on hair follicles. To investigate whether the TLR1 gene polymorphisms are associated with the development and clinical features of alopecia areata (AA), a case-control comparison of two single nucleotide polymorphisms (SNPs) (rs4833095, Asn248Ser and rs5743557, ?414C?>?T) of TLR1 were studied in 239 AA patients and 248 controls. Using multiple logistic regression model, odds ratios, 95% confidence intervals and corresponding p values were estimated. Clinical features were analyzed based on the age of onset, family history, type of AA, nail involvement and body hair involvement. The missense SNP rs4833095 was significantly associated with the development of AA (codominant2, p?=?0.002; recessive, p?=?0.001; log-additive, p?=?0.0071; and allele frequency, p?=?0.0066). The promoter SNP rs5743557 was weakly associated with the development of AA (codominant2, p?=?0.019; recessive, p?=?0.032; log-additive, p?=?0.020; and allele frequency, p?=?0.03). In the clinical features, rs4833095 was only weakly associated with age of onset between 15 and 50 years (codominant2, p?=?0.043 and recessive, p?=?0.022). The results suggest that rs4833095 of TLR1 may be associated with the susceptibility for AA in the Korean population.     

FOXP3基因多态性与斑秃的关联研究

目的探讨FOXP3基因多态性与斑秃(alopecia areata,AA)发生发展的关系。方法选择240例斑秃患者及248例正常对照。结合HapMap网站中汉族人群资料,选取rs3761547和rs3761548共2个单核苷酸多态性(single nucleotide polymorphism,SNP)位点,采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)的方法进行基因分型,统计学分析单核苷酸多态性。结果与正常对照比较,斑秃患者组FOXP3基因rs3761548位点的基因型分布有差异,具有统计学意义(P=0.015);而rs3761547位点的基因型分布在正常对照组与斑秃患者组之间没有差异(P=0.12)。非条件Logistic回归分析显示,rs3761548位点的CC基因型相对于AA和AC基因型来说,对斑秃的发病具有保护效应(adjusted OR:0.69;95%CI:0.48-0.98)。单倍型分析结果显示,与对照组相比较,斑秃患者单倍型GA和单倍型GC的分布存...     

Depression in late life: age of onset as marker of a subtype

Late-onset depression may be pathogenetically and prognostically distinct from early-onset, recurrent affective disorder. The authors reviewed records of 94 consecutively admitted unipolar major depressives over the age of 60 years, divided subjects into groups based on their age of onset, and examined demographic and clinical features. Late-onset elderly depressives had a lower incidence of family history of affective illness, longer hospital stay, and more residual symptoms at discharge. However, there was no demonstrable relationship between age of onset and presence of psychosis, melancholia, medical illness, symptom severity at admission, or indicators of neuropathology. Although late-onset elderly depressives did less well than those with early-onset illness, the data do not support the notion of late-onset depression as a distinct pathological process.     

Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation

BACKGROUND: Asthma is a heterogeneous process, yet little is understood regarding phenotypes. OBJECTIVE: To determine whether phenotypic differences exist between early-onset, severe asthma as compared with late-onset disease and whether the presence or absence of eosinophilia influences the phenotypes. METHODS: Cross-sectional analysis of integrated clinical, physiologic, and pathologic data collected from 80 subjects with severe asthma. Subjects were divided into those with asthma onset before age 12 years (n = 50) versus after age 12 (n = 30) and by the presence or absence of lung eosinophils. RESULTS: Subjects with early-onset, severe asthma had significantly more allergen sensitivity (skin test positivity, 98% vs 76%, P <.007) and more allergic symptoms (P values all 相似文献   

Association of HSPA1B SNP rs6457452 with Alopecia Areata in the Korean Population

The heat shock 70?kDa protein 1B (HSPA1B), which has been well-studied among the famous heat shock proteins HSPA1A/B/L, is related to autoimmune diseases, including Alopecia Areata (AA). In this study, the association of a 5’-untranslated region (5’UTR) SNP rs6457452 and a promoter SNP rs2763979 (‐1140C?>?T) of HSPA1B with AA was investigated in 236 controls and 228 AA patients. Statistical analyses using the multiple logistic models were done, according to the onset and the clinical features of AA, including the age of onset, family history, type of AA lesion, nail involvement and body hair involvement. The results showed that rs6457452 was associated with the onset of AA (p?<?0.002). In the analysis of clinical features of AA, rs6457452 was weakly related to the age of onset (p?≤?0.04) and that rs2763979 was only weakly related to the type of AA lesion (p?=?0.041). In conclusion, we suggest that the 5’UTR SNP rs6457452 of HSPA1B may be associated with the onset of AA and the T allele of rs6457452 may confer the reduced susceptibility to AA in the Korean population.     

Common phenotype and different non-HLA genes in Graves’ disease and alopecia areata

Our previous observations clarified that Graves’ disease (GD) is the most frequent autoimmune disease in patients with alopecia areata (AA), and 42.7% of patients with AA were positive for thyrotropin receptor antibody (TRAb). A class II HLA haplotype DRB1¹15:01-DQB1¹06:02 was suggested to contribute to autoimmunity against the thyroid gland in AA. To further clarify the genetic factors contributing to organ specificity in autoimmune diseases, we studied the contribution of non-HLA genes to organ specificity in GD and AA. A high frequency of AA (13.4%) was observed in patients with GD, indicating strong phenotypic association between GD and AA. CTLA4 and TSHR were significantly associated with GD (Pc = 0.007 and Pc < 0.002, respectively), but not with AA, even in TRAb-positive patients. The difference in the association between GD and AA suggests that the CTLA4 and TSHR are not main factors contributing to determining common genetic basis among GD and AA.     

Risk factors and characteristics of early-onset asthma in Taiwanese children.

BACKGROUND AND PURPOSE: Early-onset asthma has been reported to be associated with a family history of allergy and exposure to environmental factors. This study was designed to evaluate the relationship between age of onset of asthma and genetic and environmental factors with asthma severity in Taiwanese children. METHODS: A group of 352 children with asthma (220 males and 132 females), ranging in age from 5 to 15 years, were enrolled in this study. The subjects were divided into 2 groups: early-onset asthma (up to and including age 3) and late-onset asthma. General characteristics including family history of allergies and exposure to domestic pets and tobacco smoke were recorded. The subjects underwent pulmonary function testing and analysis of serum immunoglobulin E (IgE), eosinophil counts, and specific IgE for common allergens. RESULTS: Early-onset asthma was present in 149 subjects and late-onset asthma in 203. Family history of allergies included a sibling with asthma or urticaria predisposed to early-onset asthma (asthma, p=0.034; urticaria, p=0.024). Food and milk allergen sensitization were more common in early-onset asthma (food allergens, p=0.025; milk, p=0.034). Children with early-onset asthma had higher eosinophil counts (p=0.041). However, there was no correlation between age at onset and pulmonary function testing, the levels of total IgE and IgE specific for Dermatophagoides pteronyssinus or Dermatophagoides farinae. CONCLUSIONS: A history of asthma or urticaria in a sibling is a risk factor for early-onset asthma. A greater prevalence of food allergen sensitization and high eosinophil counts are characteristic of early-onset disease.     

The protective role of the HLA-DR locus in patients with various clinical types of alopecia areata

One of the genetic factors associated with the development of alopecia areata (AA) is the HLA locus. The study comprised 52 patients with AA aged 10 to 64 years. The frequences of HLA-DRB alleles in the patients and controls were compared. The control group comprised 152 healthy persons. Familial occurrence of AA was seen in 7 (13.5%) cases. A significantly lower frequency of HLA-DRB1*03 was observed in patients with AA comparison with the control group. In all patients with AA, alleles HLA-DRB1*15/*16 occurred more frequently than in the control group, but this was not significant after correction. In the group of patients with more severe forms of alopecia areata (alopecia areata totalis/alopecia areata universalis) there was no significant difference in HLA-DR allele distribution.     

Analysis of the monocyte chemoattractant protein 1 -2518 promoter polymorphism in Korean patients with alopecia areata

Monocyte chemoattractant protein-1 (MCP-1) levels are increased in scalp lesions of patients with alopecia areata (AA), suggesting a role in the development of AA. Recently, a biallelic A/G polymorphism in the MCP-1 promoter at position -2518 has been found, influencing the level of MCP-1 expression in response to an inflammatory stimulus. We investigated whether the presence of these polymorphisms were associated with AA in Korean population. 145 Korean patients with AA, 246 healthy subjects without clinical evidence of AA were screened for genotype with a PCR-based assay. In the AA patients the frequency of the A and G alleles was 40.3 and 59.7%, respectively and the distribution of the A/A, A/G and G/G genotypes was 19.3, 42.1 and 38.6%, respectively. Amongst the controls the frequency of the A and G alleles was 39.8 and 60.2%, and the distribution of the A/A, A/G, G/G genotypes in the same group was 17.5, 44.7 and 37.8%, respectively. There was no significant difference in the allele frequencies and genotype distributions between the patients and the controls (p=0.889, p=0.848, respectively). Our data indicates that no association exists between the -2518A/G polymorphism of the MCP-1 gene and susceptibility to alopecia areata.     

Dysthymic disorder: clinical characteristics in relation to age at onset

BACKGROUND: The variability in the clinical presentation of dysthymia has given rise to a rich debate in literature, and various hypotheses have been proposed. One is that the clinical presentation differs in relation to age at onset. The aim of the study was to evaluate differences in socio-demographic and clinical characteristics in a sample of patients with dysthymia (DSM-IV), in relation to age at onset. METHOD: 84 consecutive outpatients with a diagnosis of dysthymia (DSM-IV) were studied. All subjects were evaluated by a semistructured clinical interview and the following rating scales: HAM-A, HAM-D, MADRS, Paykel's Interview for Recent Life Events. RESULTS: 23.8% of the sample had early-onset (<21 yrs) dysthymia. Patients with early-onset disorder were significantly younger at the observation, more frequently female and single. They had a significantly longer duration of illness and in a significantly higher percentage had already received a specialist treatment before admission in the present trial. No differences in the frequency of symptoms were observed. A significantly higher percentage of patients with late-onset disease reported at least one stressful event in the year preceding the onset of dysthymia. A positive history of major depression was significantly more common among the early-onset group; social phobia, panic disorder and conversive disorder were also more frequent in this group. The late-onset patients frequently presented generalized anxiety disorder, substance abuse and somatization disorder. LIMITATION: The study is retrospective and enrolls a limited number of cases. CONCLUSIONS: The present study agrees with other reports on the differences in clinical presentation of dysthymia according to age at onset. Although they are not actually related to age at onset, some interesting findings emerged in the symptomatological characterization of the disorder, referring to the diagnostic criteria proposed in DSM-IV.     

Hostile personality characteristics, dysthymic states and neurotic symptoms in urticaria, psoriasis and alopecia

Three experimental groups of patients with urticaria, psoriasis and alopecia were compared for hostile personality characteristics, states of anxiety and depression, neurotic syndromes and stress with a control group of patients with other skin diseases. The patients from each experimental group were found to be less dominant, more intropunitive, more extrapunitive and more neurotic than the control group. The following neurotic syndromes differentiated the experimental groups: non-specific anxiety states in urticaria patients; neurotic depression in the patients with alopecia, and a variety of neurotic syndromes in the psoriasis patients. All experimental groups scored significantly higher than the controls in stress experienced during the year preceding the onset or the exacerbation of the illness.     

神经源分化因子基因多态性与2型糖尿病的关联性研究

目的　探讨神经源分化因子 (neurogenic differentiation factor 1,Neuro D)基因多态性与 2型糖尿病发生的关联性。方法　运用错配聚合酶链反应 -限制性片段长度多态性方法检测了中国湖北地区汉族 32 4例 2型糖尿病 (其中以发病年龄 40岁为界 ,分为早发及晚发两组 )及 12 4名正常对照者 ,Neuro D基因第 45位密码子碱基变异 (GCC→ ACC)。结果　 Neuro D基因在所测人群中未发现有纯合变异者。在早发 2型糖尿病组 ,其 AT基因型频率为 2 6 .8% ,与正常对照组 (10 .5 % )及晚发 2型糖尿病组 (11.6 % )比较 ,差异有显著性 (分别为χ2 =7.85 ,P=0 .0 0 5 ;χ2 =8.81,P=0 .0 0 3) ;Thr45等位基因频率在早发 2型糖尿病组及正常对照组、晚发 2型糖尿病组分别为 13.4%、5 .2 %和 5 .8% ,差异亦有显著性 (χ2 =7.15 ,P=0 .0 0 8;χ2 =8.13,P=0 .0 0 4) ;晚发 2型糖尿病组与正常对照组比较 ,Ala45 Thr基因型频率 (11.6 % vs10 .5 % ,P>0 .0 5 )及等位基因频率 (5 .8% vs 5 .2 % ,P>0 .0 5 )差异不明显 ,Thr45等位基因与早发 2型糖尿病发生相关 (OR=2 .5 2 ,95 % CI:1.42～ 4.49) ;基因型为 AT型的 2型糖尿病患者其空腹血浆 C肽水平较 AA型患者低 ,差异有显著性 (P<0 .0 5 )。结论　 Neuro D基因多态性与早发 2型糖尿     

Object relations and reality testing in early- and late-onset schizophrenia

One hundred fifty-seven U.S. military veterans with schizophrenia were divided into early-onset (i.e., onset at age 20 or before, n = 36) and late-onset (i.e., onset after age 30, n = 28) groups and completed the Bell Object Relations and Reality Testing Inventory (BORRTI), the Positive and Negative Syndrome Scale, and several representative neuropsychological instruments. Participants were compared on background characteristics and test measures. The early-onset group demonstrated significantly more object-relations and reality-testing deficits than the late-onset group. In contrast, no significant group differences were found on symptom or neuropsychological variables. An a posteriori three-group analysis that included the middle age of onset group (i.e., ages 21 to 30) found that the middle group had mean values that fell between early- and late-onset groups on most variables. No distinct patterns of BORRTI subscale scores distinguished the middle group. The finding that object-relations and reality-testing deficits are more pronounced in early-onset schizophrenia has implications for the treatment and rehabilitation of schizophrenia.     

缺血性脑卒中后癫痫发作的临床特点及治疗研究

缺血性脑卒中在脑血管疾病中较为常见,其发病率在神经科中高居首位,致残率与致死率均较高,患者多为中老年人,发病后对患者的健康与安全均危害严重。伴随着人口老龄化的加剧,脑血管疾病患病率不断升高,导致缺血性脑卒中后癫痫的患病风险也相继提升。尽管近年来临床对于脑卒中疾病管理方面取得明显进步,但关于脑卒中后癫痫疾病相关问题的研究资料仍缺乏,对其疾病发生机制以及治疗方面仍需不断进行研究。而临床上依据脑卒中后癫痫首次发作时间将其划分为早发性与迟发性两种,对于早发性癫痫主张服用抗癫痫药物终止疾病发作,并不建议长期用药,大部分迟发性癫痫患者需长期用药,方能有效控制疾病,但不论是早发性或迟发性癫痫发作,通过合理抗癫痫药物治疗,大部分患者均可取得理想的控制效果。本研究针对缺血性脑卒中后癫痫发病机制与治疗进展等展开系统分析,旨在为缺血性脑卒中后癫痫发作的临床治疗提供科学的理论依据。     

Expanding the definition of a positive family history for early-onset coronary heart disease.

PURPOSE: Assessing familial risk for early-onset coronary heart disease (CHD) is typically limited to first-degree relatives with early-onset CHD. To evaluate the impact of additional family history, we examined the associations between various family history definitions and early-onset CHD. METHODS: By using the national HealthStyles 2003 survey data, we assessed associations between self-reported family history and personal history of early-onset CHD (diagnosed at or before age 60 years), adjusting for demographics, hypercholesterolemia, hypertension, and obesity. RESULTS: Of 4,035 respondents, 60% were female and 72% were white, with a mean age of 48.8 years; 4.4% had early-onset CHD. In addition to having at least one first-degree relative with early-onset CHD, other significant associations included having at least one first-degree relative with late-onset CHD, at least one second-degree relative with early-onset CHD, and two or more affected second-degree relatives regardless of age of onset of CHD. Early-onset stroke in at least one first-degree relative and, in women, having at least one first-degree relative with diabetes were also significantly associated with early-onset CHD. CONCLUSIONS: Family history beyond early-onset CHD in first-degree relatives is significantly associated with prevalent CHD diagnosed at or before age 60 years.     

Unipolar depression in the aged: determinants of familial aggregation.

Late-onset depression (greater than or equal to 60 years) is believed to be less associated with a risk of depression in first-degree relatives than early-onset depression. However, family studies in elderly probands fitting the current methodological standards of family studies are not available. The reported family study in geriatric inpatients with unipolar major depression (n = 92) supported the proposed relationship between age at onset and the proposed familial loading. A comparison to families of age-matched controls (n = 33) revealed that relatives of probands with late-onset depression are still at an increased risk of depression. However, late-onset depression was not more common in families of probands with late-onset depression than in families of probands with early-onset depression. Besides the age at onset, the recurrence of depressive episodes defined distinct patterns of familial aggregation.     

214例斑秃患者心理疏导疗效的初步观察

214例斑秃患者作为实验组,施以协同药物处方加上心理疏导治疗,与40例来自同一门诊斑秃组成对照组;性别、年龄、病程等与实验组有可比性,但仅施以协同药物处方治疗。一个疗程(三个月)后,两组相比,前者痊愈率及总有效率均显著高于后者,甲皱微循环改善情况亦呈同样趋势、表明心理治疗与药物治疗合用对斑秃近期疗效优于单纯药物治疗。     

Differential clinical features of late-onset panic disorder

OBJECTIVES: The aim was to analyse the sociodemographic and clinical characteristics of panic disorder (PD) in patients with a PD onset after 60 years of age, at two outpatient psychiatric clinics in Barcelona (northeastern Spain). MATERIAL AND METHODS: All patients presenting with PD at two outpatient clinics over a 4-year period were assessed by the same team. Patients with PD onset at 60 or after were grouped (late-onset), and compared with the group with an earlier onset. The instruments administered to the sample were: Global Assessment of Functioning scale, Panic-Associated Symptom Scale, Hamilton's Depression and Anxiety Scales and Marks-Matthews' Fear and Phobia scale. RESULTS: Of 5301 patients attended over a 4-year period, 64 (1.2%) were PD patients aged 60 or above. Age at PD onset was over 60 in 27 cases (0.4% of the total population, and 6.1% of all PD patients). The mean age in the late-onset group was 67.0+/-4.9 years. Late-onset PD patients were less likely to report family history of PD. They scored lower on most scales assessing clinical severity (excepting GAF and agoraphobia scores), and they exhibited fewer and milder panic symptoms during the attacks. However, dysthymic disorder, but not major depressive disorder, was more common among late-onset PD patients (P<0.05). COMMENTS: The most notable findings in our late-onset PD subgroup of patients were: lesser severity of the disorder, greater comorbidity with dysthymia, and less family history of PD. Prevalence rates of late-onset PD in our sample appeared to be rather high. Physical illness and less severe panic symptoms may contribute to underdiagnosing PD in this particular subpopulation.     

Estrogen-related alopecia due to polycystic ovaries in a terrier dog

Sex hormone-related alopecia is a rare clinical condition in dogs. A 9-year-old female dog was presented with a history of symmetrical alopecia on the caudal aspects of both thighs. A dermatophyte culture, skin scrapes, and acetate strip examinations were negative for dermatophytes, parasites, and yeasts. The only abnormality in abdominal ultrasonography was multiple cystic follicles within the ovaries. This increased the possibility of hyperestrogenism due to ovarian cysts. Serum estrogen assay indicated elevated estrogen concentration. Ovariohystorectomy was performed and tissue samples of uterus, ovaries, and skin biopsies were submitted for histopathological examination. In histological examination, the polycystic ovary was characterized by multiple follicular cysts. Results of histopathological findings in skin biopsies were similar to that reported with hyperestrogenism. In view of information achieved from the presented case, hyperestrogenism should be included in the differential diagnosis for dogs with clinical manifestation of symmetrical alopecia.     

Age at onset in geriatric depression: relationship to clinical variables

The significance of age at onset of first depressive episode was evaluated in an elderly depressed population. A prospective study of 71 consecutively admitted inpatients with a diagnosis of major unipolar depression examined the relationship between age at onset of illness and several clinical variables. Subjects divided into early-onset (EO) and late-onset (LO) groups, matched for current age, did not significantly differ in terms of symptomatology, cognitive impairment, physical illness, family history or treatment responsivity. These findings do not support a nosologic separation of EO and LO depression in geriatric patients.