Nerve growth factor gene polymorphisms may be associated with heroin dependence in women but do not mediate specific personality traits.

Kuo SC ，Lin CL ，Tsou CC ，Yeh YW ，Yang BZ ，Chen CY ，Huang CY ，Huang SY ... -  《-》

The role of personality traits and life stress in alcohol use disorder: Insights from NGF gene polymorphisms of Han Chinese population in Taiwan.

Alcohol use disorder (AUD) is a complex neuropsychiatric condition influenced by genetic and environmental factors. Nerve growth factor (NGF) plays a crucial role in neuronal neuroplasticity and chronic alcohol consumption may alter NGF levels in specific brain regions. The study investigates the associations between NGF gene polymorphisms, susceptibility to AUD, and specific stress and personality characteristics. Our study involved 1133 participants from a homogeneous Han Chinese population, 587 of whom had AUD and 546 were controls. To minimize potential confounding factors, the AUD group was stratified by sex and age at baseline. A total of 414 participants completed the Life Event Questionnaires (LEQ), while 559 participants completed the Tridimensional Personality Questionnaire (TPQ). The NGF's rs7523654 and rs11102929 loci were significantly associated with AUD, especially in female subgroups. Additional haplotype research confirmed similar findings. AUD patients showed more vital propensities for novelty seeking (NS) and harm avoidance (HA) compared to controls. Additionally, they recorded higher negative LEQ results. Notably, HA and negative LEQ scores among AUD people were significantly affected by the SNP rs11102929 in the NGF gene. The age at which AUD first manifested and NS scores showed a reverse link, suggesting that a higher NS characteristic may predispose people to develop AUD earlier in life. The findings suggest that the NGF gene may influence AUD susceptibility and its links to personality traits and life stress. However, the small sample of women with AUD limits the reliability of these associations, highlighting the need for further study.

Kuo SC ，Lin CL ，Yeh YW ，Chen CY ，Huang YC ，Chang TY ，Yang YP ，Huang JS ，Yang BZ ，Huang SY ... -  《-》

STAT4 gene polymorphism may be associated with microscopic polyangiitis susceptibility in a Chinese Guangxi population: A case-control analysis based on propensity score matching.

Microscopic polyangiitis (MPA) is a severe multisystem autoimmune disease featured by small-vessel vasculitis with few or no immune complex, also has a significant genetic predisposition. Growing evidence has confirmed that STAT4 gene is tightly associated with multiple autoimmune diseases, but its contribution to MPA onset is still elusive. The aim was to investigated the association between STAT4 gene polymorphisms (rs7572482, rs7574865 and rs12991409) and MPA susceptibility in a Guangxi population of China. 260 MPA patients and 295 healthy adult volunteers were selected, 1:1 propensity score matching (PSM) was performed to control potential confounding variables, then 199 MPA patients and 199 healthy adult volunteers matched in gender, ethnicity and age were included in this study. High-throughput sequencing and multiplex PCR were applied to detect the target STAT4 SNPs. SHEsis and SNPstats were used to evaluated the allele frequency, genotype frequency, linkage disequilibrium (LD), haplotype, and the association between SNPs and the MPA susceptibility in multiple genetic models. SNP-SNP interactions were explored based on generalized multifactor dimensionality reduction (GMDR) algorithm. Some clinical indicators, such as renal pathology and therapeutic effects, were collected and compared. The allele and genotype frequencies of rs7574865 displayed significant diversities between case group and control group (p < 0.05). Strong LD was found between rs7572482 and rs12991409 (D'=0.9). The haplotype GGT was related to a reduced risk of MPA (OR = 0.661, 95 %CI: 0.469-0.931, p = 0.017), and haplotype GTT might perform an increased risk of MPA (OR = 1.922, 95 %CI: 1.225-3.015, p = 0.004). Rs7574865 polymorphism was associated with an increased risk of MPA in codominant model (OR:2.03; p = 0.0093), dominant model (OR: 1.88p = 0.0023), and overdominant model (OR:1.57; p = 0.027). In Han and male subgroups, rs7574865 polymorphism dramatically increased the MPA risk. GMDR suggested that STAT4 rs7574865 and PTPN22 rs3811021 composed the most risk combinations (p = 0.0010). Moreover, renal pathology, Birmingham vasculitis activity score (BVAS), and alanine aminotransferase (ALT) might be linked with STAT4 gene polymorphisms (p < 0.05). The genetic polymorphism of STAT4 may be associated with MPA susceptibility and renal pathological classification in Chinese Guangxi population; the T allele of rs7574865 may be an important risk factor for MPA.

Lu S ，Zhong H ，Liu F ，Zhou K ，Tang W ，Yang B ，Li W ，Xue C ... -  《-》

Sex as a prognostic factor for mortality in adults with acute symptomatic pulmonary embolism.

Pulmonary embolism (PE) is relatively common worldwide. It is a serious condition that can be life-threatening. Studies on the relationship between adverse outcomes of this condition and whether a patient is male or female have yielded inconsistent results. Determining whether there is an association between sex and short-term mortality in patients with acute PE is important as this information may help guide different approaches to PE monitoring and treatment. To determine whether sex (i.e. being a male or a female patient) is an independent prognostic factor for predicting mortality in adults with acute symptomatic pulmonary embolism. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register up to 17 February 2023. We scanned conference abstracts and reference lists of included studies and systematic reviews. We also contacted experts to identify additional studies. There were no restrictions with respect to language or date of publication. We included phase 2-confirmatory prognostic studies, that is, any longitudinal study (prospective or retrospective) evaluating the independent association between sex (male or female) and mortality in adults with acute PE. We followed the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) and the Cochrane Prognosis Methods Group template for prognosis reviews. Two review authors independently screened the studies, extracted data, assessed the risk of bias according to the Quality in Prognosis Studies (QUIPS) tool, and assessed the certainty of the evidence (GRADE). Meta-analyses were performed by pooling adjusted estimates. When meta-analysis was not possible, we reported the main results narratively. We included seven studies (726,293 participants), all of which were retrospective cohort studies with participants recruited and managed in hospitals between 2000 and 2018. Studies took place in the USA, Spain, and Japan. Most studies were multicentre. None were conducted in low- or middle-income countries. The participants' mean age ranged from 62 to 69 years, and the proportion of females was higher in six of the seven studies, ranging from 46% to 60%. Sex and gender terms were used inconsistently. Participants received different PE treatments: reperfusion, inferior vena cava filter, anticoagulation, and haemodynamic/respiratory support. The prognostication time (the point from which the outcome was predicted) was frequently omitted. The included studies provided data for three of our outcomes of interest. We did not consider any of the studies to be at an overall low risk of bias for any of the outcomes analysed. We judged the certainty of the evidence as moderate to low due to imprecision and risk of bias. We found moderate-certainty evidence (due to imprecision) that for female patients there is likely a small but clinically important reduction in all-cause mortality at 30 days (odds ratio (OR) 0.81, 95% confidence interval (CI) 0.72 to 0.92; I2 = 0%; absolute risk difference (ARD) 24 fewer deaths in women per 1000 participants, 95% CI 35 to 10 fewer; 2 studies, 17,627 participants). However, the remaining review outcomes do not indicate lower mortality in female patients. There is low-certainty evidence (due to serious risk of bias and imprecision) indicating that for females with PE, there may be a small but clinically important increase in all-cause hospital mortality (OR 1.11, 95% CI 1.00 to 1.22; I2 = 21.7%; 95% prediction interval (PI) 0.76 to 1.61; ARD 13 more deaths in women per 1000 participants, 95% CI 0 to 26 more; 3 studies, 611,210 participants). There is also low-certainty evidence (due to very serious imprecision) indicating that there may be little to no difference between males and females in PE-related mortality at 30 days (OR 1.08, 95% CI 0.55 to 2.12; I2 = 0%; ARD 4 more deaths in women per 1000 participants, 95% CI 22 fewer to 50 more; 2 studies, 3524 participants). No study data was found for the other outcomes, including sex-specific mortality data at one year. Moreover, due to insufficient studies, many of our planned methods were not implemented. In particular, we were unable to conduct assessments of heterogeneity or publication bias or subgroup and sensitivity analyses. The evidence is uncertain about sex (being male or female) as an independent prognostic factor for predicting mortality in adults with PE. We found that, for female patients with PE, there is likely a small but clinically important reduction in all-cause mortality at 30 days relative to male patients. However, this result should be interpreted cautiously, as the remaining review outcomes do not point to an association between being female and having a lower risk of death. In fact, the evidence in the review also suggested that, in female patients, there may be a small but clinically important increase in all-cause hospital mortality. It also showed that there may be little to no difference in PE-related mortality at 30 days between male and female patients. There is currently no study evidence from longitudinal studies for our other review outcomes. Although the available evidence is conflicting and therefore cannot support a recommendation for or against routinely considering sex to quantify prognosis or to guide personalised therapeutic approaches for patients with PE, this Cochrane review offers information to guide future primary research and systematic reviews.

Jimenez Tejero E ，Lopez-Alcalde J ，Correa-Pérez A ，Stallings E ，Gaetano Gil A ，Del Campo Albendea L ，Mateos-Haro M ，Fernandez-Felix BM ，Stallings R ，Alvarez-Diaz N ，García Laredo E ，Solier A ，Fernández-Martínez E ，Morillo Guerrero R ，de Miguel M ，Perez R ，Antequera A ，Muriel A ，Jimenez D ，Zamora J ... -  《Cochrane Database of Systematic Reviews》

NGF gene polymorphisms are not associated with heroin dependence in a Taiwanese male population.

Heroin dependence (HD) is a chronic relapsing brain illness with substantial heritability. Nerve growth factor (NGF) is a crucial modulator in the neurodevelopment, and may be a key mediator of reward processes in HD. The purpose of this genetic study was to investigate whether NGF gene polymorphisms associate with the occurrence of HD and the specific personality traits of patients with HD. We selected a homogeneous Han Chinese male population to overcome possible confounding effects of population and gender. For the study, 272 HD patients and 141 controls completed the Tridimensional Personality Questionnaire to evaluate their personality traits. In addition, a further sample 303 HD patients and 204 controls was added (with totally 920 participants) for the gene association and genotype-phenotype interaction studies. Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. Nonetheless, NGF gene polymorphisms did not associate with specific personality traits in HD patients and controls. There is no significant difference in NGF gene polymorphisms between patients with HD and controls. The NGF gene may neither contribute to the risk of development of HD, nor mediate the relationship between specific personality traits and HD in Han Chinese male population. Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. However, none of the polymorphisms in the NGF gene affected the NS and HA scores in both patients and healthy subjects. (Am J Addict 2018;27:516-523).

Tsou CC ，Kuo SC ，Chen CY ，Lu RB ，Wang TJ ，Huang SY ... -  《-》