Potential Susceptibility Factors Research Articles

Overview of the Genetics of Alcohol Use Disorder.

Alcohol Use Disorder (AUD) is a chronic psychiatric illness characterized by harmful drinking patterns leading to negative emotional, physical, and social ramifications. While the underlying pathophysiology of AUD is poorly understood, there is substantial evidence for a genetic component; however, identification of universal genetic risk variants for AUD has been difficult. Recent efforts in the search for AUD susceptibility genes will be reviewed in this article. In this review, we provide an overview of genetic studies on AUD, including twin studies, linkage studies, candidate gene studies, and genome-wide association studies (GWAS). Several potential genetic susceptibility factors for AUD have been identified, but the genes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), have been found to be protective against the development of AUD. GWAS have also identified a heterogeneous list of SNPs associated with AUD and alcohol-related phenotypes, emphasizing the complexity and heterogeneity of the disorder. In addition, many of these findings have small effect sizes when compared to alcohol metabolism genes, and biological relevance is often unknown. Although studies spanning multiple approaches have suggested a genetic basis for AUD, identification of the genetic risk variants has been challenging. Some promising results are emerging from GWAS studies; however, larger sample sizes are needed to improve GWAS results and resolution. As the field of genetics is rapidly developing, whole genome sequencing could soon become the new standard of interrogation of the genes and neurobiological pathways which contribute to the complex phenotype of AUD. This review examines the genetic underpinnings of Alcohol Use Disorder (AUD), with an emphasis on GWAS approaches for identifying genetic risk variants. The most promising results associated with AUD and alcohol-related phenotypes have included SNPs of the alcohol metabolism genes ADH and ALDH.

Influence of Coding Variability in APP-Aβ Metabolism Genes in Sporadic Alzheimer's Disease.

The cerebral deposition of Aβ42, a neurotoxic proteolytic derivate of amyloid precursor protein (APP), is a central event in Alzheimer’s disease (AD)(Amyloid hypothesis). Given the key role of APP-Aβ metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Aβ degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 332 sporadic and mainly late-onset AD cases and 676 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, none of which statistically significant after multiple testing correction (1.9e-4<p-value<0.05), were found to be rare coding variants (0.009%<MAF<1.4%) with moderate to strong effect size (1.84<OR<Inf) that map to genes mainly involved in Aβ extracellular degradation (TTR, ACE), clearance (LRP1) and APP trafficking and recycling (SORL1). These results were partially replicated in the gene-based analysis (c-alpha and SKAT tests), that reports ECE1, LYZ and TTR as nominally associated to AD (1.7e-3 <p-value <0.05). In concert with previous studies, we suggest that 1) common coding variability in APP-Aβ genes is not a critical factor for AD development and 2) Aβ degradation and clearance, rather than Aβ production, may play a key role in the etiology of sporadic AD.

Susceptibility Factors Relevant for the Association Between Long-Term Air Pollution Exposure and Incident Asthma.

In this review, we identified 15 studies in children and 10 studies in adults that assessed the association between long-term exposure to air pollution and incident asthma and that conducted stratified analyses to explore potential susceptibility factors. Overall, adult never-/former smokers seem to be at higher risk of incident asthma due to air pollution. Children without atopy and children from low socioeconomic status families also seem to be at higher risk of incident asthma due to air pollution. While interaction between air pollution and genes involved in the response to oxidative stress pathways have been explored, results are somewhat inconsistent and in need of replication. To evaluate interactions, large sample sizes are necessary, and much more research, including data pooling from existing studies, is needed to further explore susceptibility factors for asthma incidence due to long-term air pollution exposure.

Possible Gender-Related Modulation by the ROCK1 Gene in Colorectal Cancer Susceptibility

Aim: In view of accumulating evidence supporting a pivotal role of the Rho/ROCK pathway in cancer, we investigated Rho-kinase polymorphisms as potential susceptibility factors in colorectal cancer (CRC) in a representative sample of the Italian population. Methods: DNA obtained from the peripheral blood samples of 137 CRC patients and 141 healthy controls was genotyped for four ROCK1 (rs35996865; rs73963110; rs2127958; rs288980) and five ROCK2 (rs12692437; rs7563468; rs35768389; rs17463896; rs16857265) selected single nucleotide polymorphisms. Results: None of the allelic variants of the nine selected markers was associated with the occurrence of CRC or with the development of regional lymph node metastasis. By contrast, the ROCK1 rs35996865 G variant allele was significantly more frequent in male patients (p = 0.028) than in the control group. Conclusion: This finding is, at present, the first that points to a possible gender-related modulation by the ROCK1 gene in CRC susceptibility.

Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways

The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed for three variants, TMEM132D rs7370927 (T allele: odds ratio (OR)=1.27, 95% confidence interval (CI): 1.15-1.40, P=2.49 × 10(-6)), rs11060369 (CC genotype: OR=0.65, 95% CI: 0.53-0.79, P=1.81 × 10(-5)) and COMT rs4680 (Val (G) allele: OR=1.27, 95% CI: 1.14-1.42, P=2.49 × 10(-5)) in studies with samples of European ancestry. Nominal associations that did not survive correction for multiple testing were observed for NPSR1 rs324891 (T allele: OR=1.22, 95% CI: 1.07-1.38, P=0.002), TPH1 rs1800532 (AA genotype: OR=1.46, 95% CI: 1.14-1.89, P=0.003) and HTR2A rs6313 (T allele: OR=1.19, 95% CI: 1.07-1.33, P=0.002) in studies with samples of European ancestry and for MAOA-uVNTR in female PD (low-active alleles: OR=1.21, 95% CI: 1.07-1.38, P=0.004). No significant associations were observed in the secondary analyses considering sex, agoraphobia co-morbidity and studies with samples of Asian ancestry. Although these findings highlight a few associations, PD likely involves genetic variation in a multitude of biological pathways that is diverse among populations. Future studies must incorporate larger sample sizes and genome-wide approaches to further quantify the observed genetic variation among populations and subphenotypes of PD.

Prevalence of periodontitis in individuals with human leukocyte antigens (HLA) A9, B15, A2, and B5.

Human leukocyte antigens (HLA) have been associated with periodontitis. Previous studies revealed HLA-A9 and HLA-B15 as potential susceptibility factors, while HLA-A2 and HLA-B5 might have protective effects. The aim of the study was to verify these associations in a group of HLA-typed blood donors with previously unknown periodontal status. In four German centers, 140 blood donors with known HLA class I status were enrolled and allocated to the following five groups: HLA-A9 (N=24), HLA-B15 (N=20), HLA-A2 (N=30), HLA-B5 (N=26), and controls (N=40). Periodontal examination included the measurement of probing depths (PDs), clinical attachment level (CAL), bleeding on probing (BOP), and community periodontal index of treatment needs (CPITN). Carriers with HLA-A9 and HLA-B15 had higher values of mean PD (P<0.0001), CAL (P<0.0001), and BOP (P<0.002) as well as sites with PD and CAL with ≥4 and ≥6mm (P<0.0003), respectively, than controls. Multiple regression analyses revealed HLA-A9, HLA-B15, and smoking as risk indicators for moderate to severe (CPITN 3-4; odds ratio (OR): 66.7, 15.3, and 5.1) and severe (CPITN 4; OR: 6.6, 7.4, and 3.8) periodontitis. HLA-A2 and HLA-B5 did not show any relevant associations. The present data support a role of HLA-A9 and HLA-B15 as susceptibility factors for periodontitis, whereas HLA-A2 and HLA-B5 could not be confirmed as resistance factors. Both HLAantigens A9 and B15 are potential candidates for periodontal risk assessment.

Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pig-Tailed Macaques by Using a Systems Biology Approach.

Our earlier studies with pig-tailed macaques demonstrated various simian-human immunodeficiency virus (SHIV) susceptibilities during the menstrual cycle, likely caused by cyclic variations in immune responses in the female genital tract. There is concern that high-dose, long-lasting, injectable progestin-based contraception could mimic the high-progesterone luteal phase and predispose women to human immunodeficiency type 1 (HIV-1) acquisition and transmission. In this study, we adopted a systems biology approach employing proteomics (tandem mass spectrometry), transcriptomics (RNA microarray hybridization), and other specific protein assays (enzyme-linked immunosorbent assays and multiplex chemokine and cytokine measurements) to characterize the effects of hormonal changes on the expression of innate factors and secreted proteins in the macaque vagina. Several antiviral factors and pathways (including acute-phase response signaling and complement system) were overexpressed in the follicular phase. Conversely, during the luteal phase there were factors overexpressed (including moesins, syndecans, and integrins, among others) that could play direct or indirect roles in enhancing HIV-1 infection. Thus, our study showed that specific pathways and proteins or genes might work in tandem to regulate innate immunity, thus fostering further investigation and future design of approaches to help counter HIV-1 acquisition in the female genital tract. HIV infection in women is poorly understood. High levels of the hormone progesterone may make women more vulnerable to infection. This could be the case during the menstrual cycle, when using hormone-based birth control, or during pregnancy. The biological basis for increased HIV vulnerability is not known. We used an animal model with high risk for infection during periods of high progesterone. Genital secretions and tissues during the menstrual cycle were studied. Our goal was to identify biological factors upregulated at high progesterone levels, and we indeed show an upregulation of genes and proteins which enhance the ability of HIV to infect when progesterone is high. In contrast, during low-progesterone periods, we found more HIV inhibitory factors. This study contributes to our understanding of mechanisms that may regulate HIV infection in females under hormonal influences. Such knowledge is needed for the development of novel prevention strategies.

Correlation between ApoE gene polymorphisms and the occurrence of urolithiasis.

The aim of the present study was to investigate the correlation between apolipoprotein E (ApoE) gene polymorphisms and the occurrence of urolithiasis and dyslipidemia. A total of 180 Uyghur individuals, including 90 urolithiasis patients and 90 healthy controls, were enrolled in this study. The blood lipid profiles of the patients and controls were investigated and compared, and the composition of the urinary calculi was determined. The polymorphisms of the ApoE alleles were analyzed using polymerase chain reaction-restriction fragment length polymorphism analysis. Three common genotypes of the ApoE gene, E3/3, E3/4 and E4/4, were detected in the urolithiasis patients and control group. In the patient group, 28 patients with the E3/3 genotype (30.1%), 58 patients with the E3/4 genotype (64.4%) and four patients with the E4/4 genotype (4.5%) were identified. By contrast, in the control group, 52 patients with the E3/3 genotype (57.8%), 35 patients with the E3/4 genotype (38.9%) and three patients with the E4/4 genotype (3.3%) were identified. The frequency of the E3/4 genotype was found to be significantly higher in the patient group when compared with the control group (χ2=12.96; P<0.001). In addition, the frequency of the E4 allele was significantly higher in the patient group when compared with the control group (χ2= 6.61; P=0.025). In conclusion, the occurrence of urolithiasis was found to be associated with ApoE gene polymorphisms, and the E4 allele may be a potential susceptibility factor for urolithiasis.

Association of FXR gene variants with cholelithiasis

Impairment of bile acid homeostasis is the most important risk factor of gallstone disease. Thereby the bile acid sensor farnesoid X receptor (FXR) plays a pivotal role in hepatic and intestinal bile acid metabolism. In this explorative study, the FXR gene was investigated to identify gene variants, associated with gallstone formation in a Caucasian population. Sequencing of the FXR gene was conducted in a randomly selected cohort of gallstone carriers (n=30) and control subjects (n=16) from Stuttgart, Germany. Genomic DNA was obtained from blood leukocytes. Genotype frequencies were established in the total cohort (controls: n=133, gallstone carriers: n=74). For expression analysis, total RNA and protein were isolated from ileal biopsies. The sequencing showed the sole appearance of 10 SNPs in gallstone carriers. Further genotype analysis revealed significant gender- and weight-dependent frequency differences of 3 SNPs between gallstone carriers and controls in males (rs35724: OR=4.73, P=0.022) and normal weight subjects (rs11110385: OR=3.67, P=0.027; rs11110386: OR=3.67, P=0.027) applying the 11+12<>22 allele model. Furthermore, rs11110385 carriers showed a significantly decreased FXR protein expression (11+12<>22: P=0.003). Significant mRNA expression differences between lean rs11110385 carriers and non-carriers were observed in FXR target genes (decrease: ILBP: P=0.042, OSTalpha: P=0.071, FGF19: P=0.011. Increase: LRH1: P=0.044). Three FXR gene variants (rs35724, rs11110385, rs11110386) were identified as potential susceptibility factors for cholelithiasis in a German cohort in gender- and weight-dependent manners. Thereby the tag SNP rs11110385 seemed to influence the activation of the FXR gene.

남녀 유아의 어머니-유아 친밀감과 또래수용 간 관계에서 부정적 정서성의 조절영향

The purpose of this study was to investigate the moderating effect of negative emotionality on the association between mother-child intimacy and peer acceptance based on differential susceptibility model. According to differential susceptibility model, negative emotionality and difficult temperament is potential differential susceptibility factors. The participants were 3-year-old children recruited from preschools and daycare centers. Teachers completed measurement of negative emotionality. Peer acceptance was measured by peer nomination. Mother-child intimacy was reported by mothers. The results presented that negative emotionality significantly moderated the relation between mother-child intimacy and peer acceptance only for boys. For boys with high level of negative emotionality, mother-child intimacy significantly predicted peer acception. However, for boys with low level of negative emotionality, mother-child intimacy did not associate with peer acception. For girls, negative emotionality did not significantly influence the association between mother-child intimacy and peer acceptance. These findings support differential susceptibility hypothesis that vulnerable children are susceptible to positive parenting effects.

PROTEIN DISULFIDE ISOMERASE LIKE 5-1is a susceptibility factor to plant viruses

Protein disulfide isomerases (PDIs) catalyze the correct folding of proteins and prevent the aggregation of unfolded or partially folded precursors. Whereas suppression of members of the PDI gene family can delay replication of several human and animal viruses (e.g., HIV), their role in interactions with plant viruses is largely unknown. Here, using a positional cloning strategy we identified variants of PROTEIN DISULFIDE ISOMERASE LIKE 5-1 (HvPDIL5-1) as the cause of naturally occurring resistance to multiple strains of Bymoviruses. The role of wild-type HvPDIL5-1 in conferring susceptibility was confirmed by targeting induced local lesions in genomes for induced mutant alleles, transgene-induced complementation, and allelism tests using different natural resistance alleles. The geographical distribution of natural genetic variants of HvPDIL5-1 revealed the origin of resistance conferring alleles in domesticated barley in Eastern Asia. Higher sequence diversity was correlated with areas with increased pathogen diversity suggesting adaptive selection for bymovirus resistance. HvPDIL5-1 homologs are highly conserved across species of the plant and animal kingdoms implying that orthologs of HvPDIL5-1 or other closely related members of the PDI gene family may be potential susceptibility factors to viruses in other eukaryotic species.

Sodium Excretion and Risk of Developing Coronary Heart Disease

Despite compelling evidence for sodium's adverse effects on blood pressure, it remains uncertain whether excess sodium intake is a risk factor for coronary heart disease (CHD) in the overall population and in potentially more susceptible subgroups. We prospectively followed 7543 adults aged 28 to 75 years and free of cardiovascular and kidney disease in 1997/1998 of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Sodium excretion was measured in two 24-hour urine collections at baseline. Potential susceptibility factors were blood pressure and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median 24-hour sodium excretion was 137 mmol (Q1-Q3, 106-171 mmol). During a median follow-up of 10.5 (Q1-Q3: 9.9-10.8) years, 452 CHD events occurred. In the entire cohort, there was no association between each 1-g/d (43 mmol/24 h) increment in sodium excretion and CHD risk (adjusted hazard ratio, 1.07; 95% confidence interval, 0.98-1.18; P=0.15). However, the association of sodium excretion with CHD risk tended to be modified by mean arterial pressure (Pinteraction=0.08) and was modified by NT-proBNP (Pinteraction=0.002). When stratified, each 1-g/d increment in sodium excretion was associated with an increased risk for CHD in subjects with hypertension (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; n=2363) and in subjects with NT-proBNP concentrations above the sex-specific median (adjusted hazard ratio, 1.16; 95% confidence interval, 1.03-1.30; n=3771). Overall, there was no association between sodium excretion and risk of CHD. The association between sodium excretion and CHD risk was modified by NT-proBNP. Higher sodium excretion was associated with an increased CHD risk among subjects with increased NT-proBNP concentrations or with hypertension.

Genetics of acute and chronic pancreatitis: An update.

Progress made in identifying the genetic susceptibility underlying acute and chronic pancreatitis has benefitted the clinicians in understanding the pathogenesis of the disease in a better way. The identification of mutations in cationic trypsinogen gene (PRSS1 gene; functional gain mutations) and serine protease inhibitor kazal type 1 (SPINK1 gene; functional loss mutations) and other potential susceptibility factors in genes that play an important role in the pancreatic secretory functions or response to inflammation during pancreatic injury has changed the current concepts and understanding of a complex multifactorial disease like pancreatitis. An individual's susceptibility to the disease is governed by genetic factors in combination with environmental factors. Candidate gene and genetic linkage studies have identified polymorphisms in cationic trypsinogen (PRSS1), SPINK1, cystic fibrosis trans-membrane conductance regulator (CFTR), Chymotrypsinogen C (CTRC), Cathepsin B (CTSB) and calcium sensing receptor (CASR). Individuals with polymorphisms in the mentioned genes and other as yet identified genes are at an enhanced risk for the disease. Recently, polymorphisms in genes other than those involved in "intra-pancreatic trypsin regulatory mechanism" namely Claudin-2 (CLDN2) and Carboxypeptidase A1 (CPA1) gene have also been identified for their association with pancreatitis. With ever growing number of studies trying to identify the genetic susceptibility in the form of single nucleotide polymorphisms, this review is an attempt to compile the available information on the topic.

Genetic variation in the lymphotoxin-α (LTA)/tumour necrosis factor-α (TNFα) locus as a risk factor for idiopathic achalasia

BackgroundIdiopathic achalasia is a rare motor disorder of the oesophagus characterised by neuronal loss at the lower oesophageal sphincter. Achalasia is generally accepted as a multifactorial disorder with various genetic...

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands / SOMATSKE MUTACIJE I ANALIZA POLIMORFIZAMA U PLEOMORFNIM ADENOMIMA PLJUVAČNIH ŽLEZDA

Summary Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomor- phic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce. Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detec- tion). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes). Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p&lt;0.001). Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c- myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter poly- morphisms represent susceptibility factors for the develop- ment of PAs in the Serbian population.

Ozone short-term exposure and acute coronary events: A multicities study in Tuscany (Italy)

ObjectiveMany studies have investigated the potential role of ozone exposure in cardiovascular mortality and morbidity. The effects on specific cardiovascular outcome and the role of individual susceptibility are less studied. This paper focuses on the short-term effects of ozone on acute coronary events and it investigates comorbidities as indicators of personal susceptibility. Setting and patientsThis study was conducted in five urban areas of the Tuscany region (Italy) covering the period January 2002–December 2005. Air quality and meteorological data from urban background monitoring sites were collected. Hospital admissions for acute myocardial infarction and out-of-hospital coronary deaths were extracted from administrative database. DesignBoth time series and case-crossover designs were applied. The confounding effects of some time-dependent variables, such as temperature, were taken into account. Some potential susceptibility factors were investigated. Pooled estimates were derived from random-effect meta-analysis. ResultsDuring the warm season 4555 hospitalized acute myocardial infarctions and 1931 out-of-hospital coronary deaths occurred. Authors estimated a 6.3% (95% confidence interval, 1.2%, 11.7%) increase in out-of-hospital coronary deaths for a 10μg/m3 increase in ozone (lag0–5). Results also suggested higher risks for females, elderly, and patients previously hospitalized for cerebrovascular and artery diseases. ConclusionsThis study adds further evidence to the relation between cardiovascular diseases and ozone exposure, showing an adverse effect on out-of-hospital coronary deaths, but not on hospitalized acute myocardial infarctions. Some susceptible subgroups, such as females, elderly, and patients affected by some chronic diseases, are likely to be at major risk.

AB0253 The association of the IL1B and TNFα gene polymorphism with juvenile arthritis

BackgroundThe juvenile (idiopathic) arthritis (JIA) is one of the most common groups of pediatric rheumatic diseases. JIA, as defined by the ILAR, include 7 disease subtypes. Both genetic and environmental...

Correction: Shorter Telomere Length - A Potential Susceptibility Factor for HIV-Associated Neurocognitive Impairments in South African Woman

Correction: Shorter Telomere Length - A Potential Susceptibility Factor for HIV-Associated Neurocognitive Impairments in South African Woman

Help Me Play! Parental Behaviors, Child Temperament, and Preschool Peer Play

Social competence is a critical developmental milestone for preschoolers. Because play is the primary activity through which preschoolers interact socially with peers, it serves as an excellent indicator of social competence. The development of social competence in preschoolers is complex and multifaceted. In order to capture this complexity, we used Belsky’s differential susceptibility hypothesis as a framework for examining the contributions of child temperament and parenting styles in the prediction of peer interactive play behaviors. Using parent ratings of a sample of 44 preschool-age children, we hypothesized that child temperament (specifically, reactivity and regulation) acts as a susceptibility factor in the relationship between parenting styles (authoritarian and authoritative) and child peer play behaviors (disruptive and interactive). Our findings indicated that child reactivity moderated the relationship between authoritarian parenting style and both play outcomes, suggesting that reactivity serves as a potential susceptibility factor. More specifically, children with high reactivity who had more authoritarian parents demonstrated higher levels of disruptive play and lower levels of interactive play. Regulation did not act as a susceptibility factor in our sample. Findings are discussed in terms of implications for practice and in terms of an approach that considers temperament (specifically reactivity) and parenting behaviors in preschool assessment and intervention efforts. Additionally, we discuss how our findings partially support the differential susceptibility hypothesis.

Shorter Telomere Length - A Potential Susceptibility Factor for HIV-Associated Neurocognitive Impairments in South African Woman

The neuropathogenesis of the human immunodeficiency virus (HIV) may manifest as various neurocognitive impairments (NCI). HIV-positive individuals also have significantly shorter telomere length (TL) in peripheral blood mononuclear cells (PBMCs) and CD8+ T cells compared to HIV-negative individuals. Additionally, reduced TL has been found to be associated with chronic psychological stress. This study focused on the effects of HIV-infection and chronic stress associated with childhood trauma on telomere length, and investigated whether leukocyte TL (LTL), in particular, represents a risk factor for NCI. Eighty-three HIV-positive and 45 HIV-negative women were assessed for childhood trauma and were subjected to detailed neurocognitive testing. Blood from each participant was used to extract Deoxyribonucleic acid (DNA). Relative LTL were determined by performing real time quantitative PCR reactions as described by Cawthon et al. (2002). As expected, relative LTL in the HIV-positive individuals was significantly shorter than that of HIV-negative individuals (F = 51.56, p = <0.01). Notably, a significant positive correlation was evident between relative LTL and learning performance in the HIV-positive group. In addition, a significant negative correlation was observed between relative LTL and verbal fluency, but this association was only evident in HIV-positive individuals who had experienced trauma. Our results suggest that reduced LTL is associated with worse learning performance in HIV-positive individuals, indicating that TL could act as a susceptibility factor in increasing neurocognitive decline in HIV-infected individuals.