Association between interferon lambda 3 rs12979860 polymorphism and clinical outcome in dengue virus‐infected children

Single nucleotide polymorphisms (SNPs) in immune‐related genes have been shown to play a role in driving the development of the severe phenotypes of dengue virus (DENV) infection. We assessed the association between IFNL3 gene SNP (rs12979860) and dengue clinical outcomes in children. Patients with dengue‐related symptoms (aged 1–15 years) admitted at a public hospital in Northeast Brazil were invited to participate. The association between rs12979860 polymorphism and dengue classification and clinical signs and symptoms were analysed. A total of 206 DENV‐infected children were included: 53.4% of the infections were classified as severe dengue. The T allele carriers had higher risk of developing severe dengue when compared to CC genotype carriers (OR: 1.81; 95% CI: 0.98–3.32 p = .054). The T allele carriers also showed longer fever episodes when compared to patients with the CC genotype (OR: 1.90; 95%CI: 1.07–3.38; p = .027). On the other hand, the ones carrying the CT/TT genotype had 70% lower chance of developing thrombocytopenia when compared to those with the CC genotype (OR: 0.30; 95%CI: 0.08–0.88; p = .042). Our findings demonstrated that the T allele carriers of the IFNL3 gene had higher risk of developing severe dengue, suggesting a link between IFN‐λ expression and DENV immunopathogenesis.     

Antibodies play a greater role than immune cells in heterologous protection against secondary dengue virus infection in a mouse model

The four serotypes of dengue virus (DENV1–4) are causative agents of dengue fever and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Previous DENV infection is a risk factor for DHF/DSS during subsequent infection by a different serotype. Nonetheless, most primary and secondary DENV infections are asymptomatic. To investigate the possible mechanisms of immune protection in vivo, 129/Pas mice lacking IFN-α/β and -γ receptors (AG129) were used to model secondary infection using both DENV1–DENV2 and DENV2–DENV4 sequences. At intervals between sequential infections of 4 to 52 weeks, protection against secondary heterologous DENV infection was observed. Passive transfer of DENV-immune serum was protective against replication of heterologous challenge virus in all tissues tested, whereas adoptive transfer of DENV-immune cells significantly protected mice from replication of the challenge virus only when a lower inoculum was administered. These findings are relevant for understanding both natural and vaccine-induced immunity to DENV.     

Role of VEGF gene variability in longevity: a lesson from the Italian population

Vascular endothelial growth factor (VEGF) gene polymorphisms have been associated with an increased risk of developing a wide variety of disorders from diabetes to neurodegenerative diseases suggesting functions not confined to its vascular effects originally described. Based on the VEGF protective roles undisclosed in pathological conditions, we evaluate whether VEGF variability might be a determinant also for longevity. Four polymorphisms (−2578C/A, −1190G/A, −1154G/A and −634G/C) within the VEGF gene promoter region in 490 unrelated Italian healthy subjects have been analysed. Significant changes of allele, genotype (−2578/AA versus −2578/CC: OR = 2.08, p = 0.007; −1190/AA versus −1190/GG: OR = 2.01, p = 0.011) and haplotype (AAGG: 10.4% versus 14.9%, p = 0.03) frequency distributions were observed between young/elderly (25–84 years old) and long-lived (85–99 years old) subjects. These results suggest that VEGF gene variability can be inserted among the genetic factors influencing the lifespan.     

Significance of Transporter Associated with Antigen Processing 2 (<Emphasis Type="Italic">TAP2</Emphasis>) Gene Polymorphisms in Susceptibility to Dengue Viral Infection

Background and Aims The polymorphic transporter associated with antigen processing (TAP)1 and TAP2 genes encode subunits of the transporter that delivers peptides to the human leukocyte antigen class I molecules. Because the polymorphism of the TAP genes has been shown to affect peptide transport, it has been suggested that TAP genes are potential regulators of the immune response. We recently reported that TAP1 gene polymorphism is associated with severe dengue infection. This study was carried out to elucidate whether TAP2 polymorphisms are involved in diverse pathogenesis of dengue infection. Materials and Methods This study included 100 controls and 197 dengue-infected patients who were further categorized into 90 dengue fever (DF) cases, 75 dengue hemorrhagic fever cases (DHF), and 32 dengue shock syndrome (DSS) cases as per WHO grading system. TAP2 gene polymorphisms were determined by amplification refraction mutation system-polymerase chain reaction. Results The frequency of isoleucine at TAP2 379 (34.5%) was increased among DHF in comparison to controls (21%, P = 0.014). DHF cases were more likely to be heterozygous at TAP2 379 (50.7%) than controls [24%, odds ratio (OR) = 2.11, P = 0.001]. Significantly high proportion of DHF was found to have TAP2 665 threonine/alanine (THR/ALA) genotypes (30.7%) when compared with DF (13.3%, OR = 2.3, P = 0.006) cases. There was no difference in the genotypes studied between DSS and controls or DF or DHF. Conclusion This first report on TAP 2 gene polymorphism in dengue suggested that heterozygous pattern at TAP2 379 locus confers susceptibility to DHF, and TAP2 665 THR/ALA genotype was found to be a risk factor for development of DHF.     

Diversity and association of HLA/KIR receptors with type 2 diabetes in South India

The present study was undertaken to delineate the association(s) of KIR–HLA combination in South Indian Type 2 diabetes mellitus (T2DM) patients. The T2DM patients (n = 343) and healthy controls (n = 309) were genotyped for KIR/HLA ligands by PCR‐SSP method. The increased frequency of activatory KIR (aKIR) 2DS2 (OR = 1.91; p < 2.91 × 10^?4) was observed in patients suggesting a susceptible association. The frequencies of iKIR 2DL2 (OR = 0.38; p < 1.55 × 10^?5) and aKIRs 2DS1 (OR = 0.60; p < 0.001) and 3DS1 (OR = 0.52; p < 5.83 × 10^?5) were decreased in patients suggesting protective associations. The C1/C2 combinatorial analysis has revealed an increased frequency of C1⁺/C2^? in T2DM patients (OR = 1.62; p < 0.014). The KIR “AB” genotype (OR = 2.41; p < 3.87 × 10^?5) was observed to be higher in patients. However, the “BB” genotype (OR = 0.32; p < 4.71 × 10^?7) was increased in controls. The KIR motifs, “Tel‐B/B” (OR = 1.84; p < 0.007), were observed higher among patients. However, the frequency of “Tel‐A/B” motif genotype was decreased in patients (OR = 0.56; p < 3.13 × 10^?4). The iKIR/HLA combinations such as 2DL2/3 +C1 and 3DL2+A3/A11 were increased in patients (OR = 3.90; p < 7.5 × 10^?5) suggesting susceptible associations. On the contrary, the aKIR+HLA combinations such as 2DS2+C1, 2DS1+C2 and 3DS1+Bw4 were less frequent in patients (OR = 0.32; p < 4.2 × 10^?4) suggesting protective associations. Thus, the present study clearly establishes the positive and negative associations of different KIR–HLA receptor combinations with T2DM in South India.     

KIR copy number variations in dengue-infected patients from northeastern Thailand

Killer immunoglobulin-like receptors (KIRs) are a family of receptors expressed on Natural killer (NK) cells. The extensive polymorphism of KIR is involved in the immune responses of NK cells and influences dengue infections. We investigated the diversity of KIR copy numbers in dengue-infected patients from northeastern Thailand. Copy numbers of KIRs were determined by quantitative polymerase chain reaction in 137 dengue-infected patients, comprising 63 dengue fever (DF) and 74 dengue hemorrhagic fever (DHF). The distribution of KIRs was observed to be between 0 and 4 copies. The KIR AA genotype with heterozygous KIR2DS4D/WT was the most common in dengue patients, 25.4% DF and 23% DHF. Forty KIR profiles were determined in dengue patients, including 31 usual, 6 expanded, and 3 contracted profiles. Investigation of KIR copy number and dengue severity indicated that two copies of KIR2DL3 combined with HLA-C1C1 associated with an increased risk of DHF (OR 2.32, 95% CI 1.159–4.624, P = 0.016), whereas one copy of KIR2DL2 and KIR2DL3 together with HLA-C1C1 associated with a reduced risk of DHF (OR 0.17, 95% CI 0.058–0.482, P < 0.001). The outcomes of this study will contribute to the understanding of KIR complexity and innate immune responses in dengue infections.     

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population,a preliminary report

Several lines of evidence support an association between tropomyosin 1 (TPM1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present study aimed to investigate the association between TPM1 polymorphisms and the risk of NSCL/P in an Iranian population. This case‐control was done on 105 NSCL/P patients and 110 unrelated healthy controls. TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 polymorphisms were genotyped by the polymerase chain reaction‐restriction fragment length polymorphism method. The finding showed that rs11071720 polymorphism significantly increased the risk of NSCL/P in homozygous codominant (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.14–5.69, p = 0.023, TT vs. CC), recessive (OR = 2.33, 95% CI = 1.06–5.18, p = 0.021, TT vs. CT + CC), and allele (OR = 1.53, 95% CI = 1.02–2.30, p = 0.030, T vs. C). The rs12148828 polymorphism was associated with protection against NSCL/P in codominant (OR = 0.27, 95% CI = 0.15–0.48, p < 0.001, TC vs. TT) and allele (OR = 0.38, 95% CI = 0.22–0.64, p < 0.001, C vs. T). Regarding rs3803499, the findings proposed that this polymorphism significantly increased the risk of NSCL/P in codominant (OR = 3.86, 95% CI = 1.19–12.56, p = 0.025, CC vs. TT) and recessive (OR = 3.74, 95% CI = 1.09–14.15, p = 0.018, CC vs. CT + TT). No significant association was practical between rs1972041 polymorphism and NSCL/P. In conclusion, the findings proposed that TPM1 polymorphisms may contribute to the etiology of NSCL/P in a sample of the Iranian population.     

Association between CTLA-4 polymorphisms and susceptibility to Celiac disease: A meta-analysis

Objective

The study explored whether cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphisms confer susceptibility to Celiac disease (CD).

Methods

A meta-analysis was conducted on the associations between the CTLA-4 CT60 A/G, +49 A/G, −318 C/T polymorphisms and CD using allele contrast, a recessive model, a dominant model, and homozygote contrast.

Results

Thirteen separate comparison studies were considered in the meta-analysis consisting of 5072 patients with CD and 13,462 controls. All subjects were Europeans. Meta-analysis of the CTLA-4 CT60 A/G polymorphism showed an association between CD and the CTLA-4 CT60 G allele in all subjects [Odds ratio (OR) = 1.160, 95% Confidence interval (CI) = 1.104–1.219, p < 1.0 × 10⁻⁹). Meta-analysis using the recessive model also revealed an association between CD and the CTLA-4CT60 GG genotype (OR = 1.331, 95% CI = 1.093–1.620, p = 0.004). Furthermore, analyses using the dominant model and homozygote contrast showed the same pattern as that shown by the CTLA-4CT60 G allele. Meta-analysis of the CTLA-4 +49 A/G polymorphism showed no association between CD and the CTLA-4 +49 G allele in all subjects (OR = 0.992, 95% CI = 0.872–1.129, p = 0.907). Meta-analysis using the recessive, dominant model, and homozygote contrast showed the same pattern as that shown by the CTLA-4 +49 Gallele. Meta-analysis of the CTLA-4 −318 C/T polymorphism showed no association between CD and the CTLA-4 −318 T allele in all subjects (OR = 1.018, 95% CI = 0.813–1.275, p = 0.877).

Conclusions

The CTLA-4 CT60 A/G polymorphism was associated with CD susceptibility, but no association was found between CTLA-4 +49 A/G and −318 C/T polymorphisms and CD in Europeans.     

Clinical characteristics and risk factors for intracranial hemorrhage or infarction in patients with dengue

BackgroundIntracranial hemorrhage (ICH) or infarction in dengue cases is rare but very challenging for clinicians. We report these uncommon complications of dengue patients and focused on the significant factors associated with ICH or infarction in dengue patients.MethodsThis investigation was a retrospective study of 182 adult dengue patients who received brain computed tomography at three Taiwan hospitals during the 2014 and 2015 dengue outbreaks. This included 13 hemorrhage cases, 26 infarction cases and 143 cases without brain infarction or hemorrhage.ResultsAmong them, 13 (7.14%) suffered from ICH (6 had subdural hemorrhage, 3 had subarachnoid hemorrhage, 1 had subdural and subarachnoid hemorrhage, and 3 had intracerebral hemorrhage) and 26 (14.3%) had brain infarction. The overall mortality rate was 4/13 (30.8%) in the ICH group and 3/26 (11.5%) in the infarction group. The significant variables from the univariate analysis, including difference between 2014 and 2015, age, history of cerebrovascular accident, bone pain, arthralgia, dizziness, altered consciousness, and a higher Charlson comorbidity score. Multivariate analysis revealed that significant risk factors for ICH/infarction in dengue cases were the year of occurrence, 2014 vs. 2015 (p < 0.0001, OR = 25.027, 95% CI = 8.205–76.336), Charlson score >4 (p = 0.01, OR = 3.764, 95% CI = 1.364–10.386) and altered consciousness (p < 0.0001, OR = 6.3, 95% CI = 2.242–17.7). The factors physicians should notice in dengue endemic regions for brain infarction or ICH include altered consciousness and a Charlson score >4, especially in the year that a higher frequency of infarction/ICH was observed.     

TGFB1 Functional Gene Polymorphisms (C‐509T and T869C) in the Maternal Susceptibility to Pre‐eclampsia in South Indian Women

Pre‐eclampsia (PE), a pregnancy‐specific vascular disorder characterized by hypertension and proteinuria, is hypothesized to be the result of inadequate placental angiogenesis with attendant systemic inflammation. The pleiotropic cytokine, Transforming Growth Factor‐β1 (TGF‐β1), is considered to be a key candidate gene in the molecular pathogenesis of PE by virtue of its ability to not only regulate angiogenesis and apoptosis of target cells, but also by acting as a master controller of Th1/Th2 cytokine balance and production of the anti‐inflammatory peripheral regulatory T cells (FOXP3+ Tregs). Based on this presumption, we screened a total of 469 pregnant women from South India that include 239 patients with PE and 230 healthy controls for the two functional polymorphisms of TGFB1 gene (C‐509T and T869C). The genotype frequencies of these two polymorphisms differed significantly between the PE and control groups (P = 0.01 and P = 0.002, for the TGFB1 C‐509T and T869C polymorphisms, respectively). Under the over‐dominant model, the CT genotype of the TGFB1 C509T polymorphism showed a high protective effect (P = 3e‐04), while the TT genotype of the same variant appeared to be the predisposing genotype (P = 0.003). The T‐T and C‐C haplotypes were found to be the risk haplotypes blocks towards PE (OR = 4.72; P = 0.031, OR = 5.39; P = 0.03), respectively. Strong linkage disequilibrium was seen between the two polymorphisms. Our investigations revealed a significant influence of TGFB1 C‐509T and T869C polymorphisms on the PE risk in South Indian women. The study represents one of the first of its kind from the Indian subcontinent.     

SPINK5 is associated with early‐onset and CHI3L1 with late‐onset atopic dermatitis

We have recently showed that filaggrin (FLG) mutations are associated only with early‐onset of AD, but not with late‐onset of AD. Consequently, other susceptibility genes should receive attention, especially in patients with late‐onset of AD. Our aim was to assess the associations between development of AD and the polymorphisms rs2303067 in SPINK5 and rs490928 in CHI3L1. A study population of 241 AD patients and 164 healthy controls was genotyped for two polymorphisms (rs2303067 in SPINK5 and rs490928 in CHI3L1). Rs2303067 in SPINK5 was significantly associated with early‐onset AD (≤8 years: p = .003; OR = 2.57) and was characterized by the need for hospitalization (p = .006; OR = 2.76), prolonged duration (≥10 years; p = .008; OR = 2.32) and more body parts affected (p = .015; OR = 2.01). In contrast, rs490928 in CHI3L1 was associated with late‐onset AD (>8 years: p = .048; OR = 1.65) and was characterized by no need for hospitalization (p = .049; OR = 1.59), shorter duration (<10 years; p = .017; OR = 1.94) and fewer body parts affected (p = .049; OR = 1.75). Our results confirmed that different AD phenotypes, specifically early‐ and late‐onset AD, have different genetic backgrounds. Early‐onset AD was associated with rs2303067 in SPINK5, which is involved in skin barrier functioning, and late‐onset was associated with rs4950928 in CHI3L1, which is involved in the immune response. Future studies should examine the early‐ versus late‐onset subgrouping more closely.     

Mannose-binding lectin gene (MBL2) polymorphisms related to the mannose-binding lectin low levels are associated to dengue disease severity

Dengue is the main arbovirosis in the tropical and subtropical areas of the world. The majority of infected individuals present an asymptomatic outcome while others progress to dengue fever (DF) or dengue haemorrhagic fever (DHF). Dengue infection evolution to severe outcomes is in part, related to innate immunity response. The MBL2 gene encodes for a pathogen recognition pattern molecule, the mannose-binding lectin (MBL). Variant alleles at promoter and structural regions of the MBL2 are related to serum MBL levels and function. Due to the important inflammatory modulation role of MBL, MBL2 polymorphisms could influence dengue progression. Therefore, this study investigated associations of MBL2 polymorphisms and serum MBL levels in patients with dengue. Genotyping of promoter and structural regions of MBL2 was performed by real-time PCR using Taqman® probes in 161 patients presenting DF or DHF outcome. For the serum MBL determination a commercial ELISA kit was used. The variant OO genotype and O allele were associated with DHF (p = 0.008 and p = 0.009 respectively). Haplotypes correlated to MBL low levels were associated with DHF (p = 0.04). Our results support the hypothesis that patients carrying genotypes or haplotypes of low production of MBL would be more susceptible to DHF.     

Correlation of CTLA-4 polymorphism and the risk of gastric cancer in a Chinese Bai population

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is involved in the regulation of immune responses mediated by T cells. This study aimed to explore the correlation between CTLA-4 gene polymorphisms and the risk of gastric cancer (GC) in the Bai minority population of southwestern China. A total of 422 GC patients and 397 healthy controls (HC) were included in this case–control study. Four single nucleotide polymorphism sites of CTLA-4 gene (rs231775, rs733618, rs16840252 and rs3087243) were selected and analysed. The results showed a significant difference in the rs733618 loci between GC and HC groups. The frequency of the rs733618 polymorphism ‘TC’ genotype was significantly lower in GC group compared to the HC group [odds ratio (OR), 95% confidence interval (CI): .47 (.35–.63), p < .001]. GC cases with dominant genetic model ‘TC + CC’ had a 47% reduced risk of GC [OR, 95%CI: .53 (.40–.71), p < .001]. Subgroup analyses revealed that the rs733618 ‘TC + CC’ genotype was associated with a lower risk of GC in male patients [OR, 95%CI: .42 (.31–.58), p < .001], those aged ≤60 years old [OR, 95%CI: .27 (.18–.42), p < .001], non-drinkers [OR, 95%CI: .21 (.13–.33), p < .001], non-smokers [OR, 95%CI: .38 (.25–.57), p < .001] and individuals without Helicobacter pylori infection [OR, 95%CI: .16 (.10–.26), p < .001]. Further multivariated analyses indicated that individuals with the ‘TC + CC’ rs733618 genotype who were aged ≤60 years old [OR, 95%CI: .42 (.29–.83), p = .032] and had no H. pylori infection [OR, 95%CI: .35 (.28–.76), p = .018] were found to have a protective effect against GC. Additionally, soluble CTLA-4 were significantly lower in GC patients with ‘TC’ and ‘TC + CC’ genotypes (all p < .05). Our findings suggest that the rs733618 polymorphism of CTLA-4 gene may play a critical role in the prevention of GC.     

MTTP variants and body mass index, waist circumference and serum cholesterol level: Association analyses in 7582 participants of the KORA study cohort

The microsomal triglyceride transfer protein (MTTP) is a key regulator in the assembly and secretion of chylomicrons and very low density lipoprotein (VLDL) in the intestine and in liver. Associations between MTTP variants and traits of the metabolic syndrome are carried out in relatively small cohorts and are not consistent.We analysed MTTP polymorphisms in 7582 participants of the KORA study cohort. Seven htSNPs covering a 52 kb region of the MTTP locus and two cSNPs (I128T, H297Q) were selected.A MTTP haplotype containing the minor allele of H297Q showed a significant decrease of −0.636 (95% CI: −1.226, −0.046; p = 0.035) BMI units in females but not in males. In comparison to homozygous H-carriers for the major allele of the MTTP H297Q polymorphism, homozygous Q297Q carriers showed a significant decrease in BMI of −0.425 BMI units (95% CI: −0.74, −0.12; p = 0.007), in waist circumference of −0.990 cm (95% CI: 1.74, −0.24; p = 0.01) and in total cholesterol of −0.039 mmol/l (95% CI: −0.07, 0; p = 0.03). Heterozygous Q-carriers displayed a reduction in BMI of −0.183 BMI unit (95% CI: −0.33, −0.04; p = 0.012), in waist circumference of −0.45 cm (95% CI: 0.8, −0.1; p = 0.01) and in total cholesterol of −0.103 mmol/l (95% CI: −0.18, −0.03; p = 0.01). Gender stratified statistics revealed a significant reduction of −0.657 BMI units (95% CI: −1.14, −0.18; p = 0.007), −1.437 cm waist circumference (95% CI: −2.55, −0.32; p = 0.01) and −0.052 mmol/l total cholesterol (95% CI: −0.1, −0.01; p = 0.03) for females homozygous for the Q297Q polymorphism. Females carrying the Q-allele showed a decrease of −0.259 BMI unit (95% CI: −0.48, −0.04; p = 0.023), −0.662 cm waist circumference (95% CI: −1.18, −0.14; p = 0.01) and −0.111 mmol/l total cholesterol (95% CI: −0.21, −0.01; p = 0.03).Our association analysis in a large population based study cohort provides evidence that the minor allele of the MTTP H297Q polymorphism is associated with lower BMI, waist circumference and total cholesterol in females but not in males.     

High Producing Tumor Necrosis Factor Alpha Gene Alleles in Protection against Severe Manifestations of Dengue

Dengue virus (DENV) infection usually presents with mild self-limiting dengue fever (DF). Few however, would present with the more severe form of the disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In the present study, the association between IL-12B, IL-10 and TNF-α gene polymorphisms and dengue severity was investigated. Methods: A case-control study was performed on a total of 120 unrelated controls, 86 DF patients and 196 DHF/DSS patients. The polymorphisms in IL-12B, IL-10 and TNF-α genes were genotyped using PCR-RFLP and PCR-sequencing methods. Results: A protective association of TNF-α -308A allele and -308GA genotype against DHF/DSS was observed, while TNF-α -238A allele and -238GA genotype were associated with DHF/DSS. A combination of TNF-α -308GA+AA genotype and IL-10 non-GCC haplotypes, IL-12B pro homozygotes (pro1/pro1, pro2/pro2) and IL-12B 3''UTR AC were significantly correlated with protective effects against DHF/DSS. An association between the cytokine gene polymorphisms and protection against the clinical features of severe dengue including thrombocytopenia and increased liver enzymes was observed in this study. Conclusion: The overall findings of the study support the correlation of high-producer TNF-α genotypes combined with low-producer IL-10 haplotypes and IL-12B genotypes in reduced risk of DHF/DSS.     

Evaluation of TLR2, TLR4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility

Previous studies indicated that single‐nucleotide polymorphisms (SNPs) of genes coding for toll‐like receptors (TLRs) and toll‐interacting protein (TOLLIP) may be involved in the pathogenesis of pulmonary tuberculosis (PTB). This study was designed to investigate potential associations between the polymorphisms in TLR2, TLR4, and TOLLIP and susceptibility to latent tuberculosis infection (LTBI) or subsequent PTB in a Chinese Han population. A total of 209 PTB and 201 LTBI patients and 204 healthy control subjects (HCS) were enrolled in our study. We performed a logistic regression including sex and age as covariates to test the effect of genotype. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR). Eleven markers in TLR2, TLR4, and TOLLIP were assessed. No significant association between polymorphisms of TLR2 and TLR4 with PTB or LTBI was detected. For TOLLIP, rs5743899 (p = 0.005, OR = 1.83, 95% CI: 1.20–2.80) CC genotype were risk factors for PTB progression. Moreover, rs5743867 under addictive (p = 0.005, OR = 1.54, 95% CI: 1.14–2.07) and recessive model (p = 0.004, OR = 1.86, 95% CI: 1.22–2.83) were also risk factors for PTB susceptibility. Our results indicate that polymorphisms in TOLLIP affected the risk of PTB disease.     

Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Leptin is a peptide hormone secreted by adipocytes. It has been shown to modulate production and clearance of amyloid beta (Aβ) in rodent models. We sought to determine if serum leptin was associated with cognitive decline in the elderly.We studied 2871 well-functioning elders, aged 70–79, who were enrolled in a prospective study. Serum leptin concentrations were measured at baseline and analyzed by mean ± 1S.D. Clinically significantly cognitive decline over 4 years was defined as ≥5-point drop on the Modified Mini Mental State Exam (3MS).Compared to those in the lower leptin groups, elders in the high leptin group had less cognitive decline, 20.5% versus 24.7% (OR = 0.79; 95% CI 0.61–1.02, p = 0.07). After adjustment for demographic and clinical variables, including body mass index and total percent body fat, those in the high leptin group had significantly less likelihood of cognitive decline, OR = 0.66 (95% CI 0.48–0.91).We conclude that in elderly individuals, higher serum leptin appears to protect against cognitive decline, independent of comorbidites and body fat.