Infectious diseases, IL6 -174G>C polymorphism, and human development.

Interleukin-6 (IL6) is a pro-inflammatory cytokine that is required for resistance against many pathogens. However, sustained IL6 activity can cause tissue damage in the periphery and brain. Previous studies have shown that populations in disease-endemic regions adapt by selecting the high-producing G-allele at the -174G>C (rs1800795) polymorphism, while others have linked increased IL6 to cognitive impairments.

Interaction between infectious diseases and personality traits: ACP1*C as a potential mediator.

In geographical regions characterized by high pathogen prevalence, it has been shown that human populations tend to be characterized by lower levels of extraversion (E) and openness to experience (OtE). According to the "behavioral immune system" hypothesis, the reduction of extraversion and openness levels represents a behavioral defense against infections. Like the 'classical' immune system, the "behavioral immune system" could also be shaped by its underlying genetic background.

Modulation of a number of genes on personality traits in a sample of healthy subjects.

A large number of studies investigated the genetic modulation of personality with mixed results. As a confirmatory analysis of previous findings, we firstly examined the association between several previously examined single nucleotide polymorphisms (SNPs) and personality traits in a sample of 158 healthy subjects. As a secondary aim, we tested the potential modulation of additional never previously investigated genes on personality.

The gene-immune-behavioral pathway: Gamma-interferon (IFN-γ) simultaneously coordinates susceptibility to infectious disease and harm avoidance behaviors.

Cytokine gene variants are known to influence both infectious disease susceptibility and harm-avoidant behaviors, suggesting that these risk variants may be pleiotropically linked to instinctual disease-avoidant traits. The gamma-interferon (IFNG) +874 T>A polymorphism (rs2430561) is an ideal candidate gene variant for immune-behavioral studies. It is a functional SNP, regulating IFNG mRNA expression; it is known to modulate serotonergic activity and is therefore capable of modifying behavior; and it has previously been associated with increased susceptibility to malaria, tuberculosis, leprosy and Chagas disease.

GSK3β genetic variability in patients with Multiple Sclerosis.

Glycogen synthase kinase-3 beta (GSK3β) is a ubiquitous kinase that is part of multiple signaling pathways. It has neurotrophic/neuroprotective effects by mediating the actions of neurotrophic molecules in the brain, thus providing neuroprotection through modulation of energy metabolism. Notably, it has been demonstrated that GSK3β is involved in Wnt-beta-catenin signaling, which contributes to the inhibition of myelination and remyelination processes in mammals.

Maternal age at the birth of the first child as an epistatic factor in polygenic disorders.

The identification of the genes for complex, polygenic disorders has proven difficult. This is due to the small effect size of each gene and genetic heterogeneity. An additional important factor could be the presence of unidentified epistatic factors.

Risk of late-onset Alzheimer's disease associated with BDNF C270T polymorphism.

We examined the frequency of the T allele of the C270T polymorphism of the brain-derived nerve growth factor (BDNF) gene in a test and replication test design. Our objective was to determine if there is an association between the BDNF gene and Alzheimer's Disease (AD) in a US population. There were 106 autopsy-proven AD cases and 101 controls of similar ages in each test for a total of 212 AD cases and 202 controls.

RANTES: a genetic risk marker for multiple sclerosis.

Unlabelled: Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a beta-chemokine and has been detected in brain lesions of multiple sclerosis (MS) patients. Considering its potential role in MS, we screened two functional polymorphisms in the proximal promoter region of the RANTES in MS patients versus controls.

Methods: We examined 140 postmortem brain samples from subjects with a primary diagnosis of MS, and peripheral blood samples from 216 control subjects.

Association of CCR5 delta32 deletion with early death in multiple sclerosis.

Purpose: The interaction between chemokines and their receptors is extremely important in controlling T cell migration into sites of CNS inflammation. Because trafficking of inflammatory T cells into the central nervous system (CNS) is a key player in the pathogenesis of multiple sclerosis (MS), we investigated the possible association of CCR5 delta32 deletion in this disorder.

Methods: DNA isolated from postmortem brain tissue samples of 132 patients with MS and from blood tissue samples of 163 gender and ethnicity-matched healthy controls was used to screen for the CCR5 delta32 deletion allele.

A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes.

We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes mellitus (T1D). The variants encoded by the two alleles, 1858C and 1858T, differ in a crucial amino acid residue involved in association of LYP with the negative regulatory kinase Csk. Unlike the variant encoded by the more common allele 1858C, the variant associated with T1D does not bind Csk.

A multigene test for the risk of sporadic breast carcinoma.

Background: Although the identification of the BRCA1 and BRCA2 genes have been of great interest, these genes account for less than 5% of all breast carcinoma cases. The remaining cases are sporadic. Reanalysis of a large twin study suggested that genetic factors may play a significant role in sporadic breast and other carcinomas.

Association of the acid phosphatase (ACP1) gene with triglyceride levels in obese women.

The acid phosphatase (ACP1) locus codes for a low molecular weight protein tyrosine phosphatase (LMPTP) that is found ubiquitously in human tissues. The *A allele of the ACP1 gene is associated with lower total enzymatic activity than the *B and *C alleles. An association between the *A allele and extreme values of body-mass-index (BMI) and dyslipidemia has previously been described in several samples of obese subjects from the Italian population.

Association between the low molecular weight cytosolic acid phosphatase gene ACP1*A and comorbid features of Tourette syndrome.

Protein tyrosine phosphatases have been implicated in the regulation of serotonergic and dopaminergic activity in the central nervous system. In a recent study we found that nonA/nonA homozygosity at the locus codifying for the low molecular weight protein tyrosine phosphatase (ACP1) was associated with increased rates of major depression in males (P<0.00003), suggesting that the ACP1*A single nucleotide polymorphism (SNP) may be an important marker for psychopathology.

Parent-daughter transmission of the androgen receptor gene as an explanation of the effect of father absence on age of menarche.

Based on an evolutionary theory of socialization, Belsky and colleagues proposed that girls exposed to a stressful environment, especially when due to father absence in the first 7 years of life, showed an early onset of puberty, precocious sexuality, and unstable relationships as adults. The authors of this article examined an alternative explanation that a variant X-linked androgen receptor (AR) gene, predisposing the father to behaviors that include family abandonment, may be passed to their daughters causing early puberty, precocious sexuality, and behavior problems. The results of a study of 121 White males and 164 White females showed a significant association of the short alleles of the GGC repeat polymorphism of the AR gene with a range of measures of aggression and impulsivity, increased number of sexual partners, sexual compulsivity, and lifetime number of sex partners in males; and paternal divorce, father absence, and early age of menarche in females.

Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women.

Cholinergic neurons have been implicated in depression and in the disorders of REM sleep in depression. We examined a common A-> T 1890 polymorphism in the 3' UTR of the cholinergic muscarinic receptor 2 (CHRM2) gene. There was a significant increase in the frequency of 11 homozygotes in 126 women with major depression (43.

Association between the phenylethanolamine N-methyltransferase gene and multiple sclerosis.

Phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholamine biosynthesis pathway, catalyzes the conversion of norepinephrine (NE) to epinephrine (EPI). PNMT is a candidate gene for multiple sclerosis (MS) for two reasons. PNMT is known to map to a region identified in two genome screens for MS and it directly regulates the amounts of NE and EPI, both of which play a significant role in the modulation of the innate immune response.