Can we consider soluble herpes virus entry mediator (sHVEM) as a tumor marker?

Background: Immune checkpoint molecules have critical roles in directing immune responses into co-inhibitory and co-stimulatory signals. Herpes virus entry mediator (HVEM) is a receptor of tumor necrosis factor receptor superfamily with unique features due to its interaction with both inhibitory and stimulatory ligands. The aim of this study was to measure the serum level of the soluble form of HVEM in patients with gastric, colorectal and breast cancers and evaluating its diagnostic and prognostic value. Methods: The concentration of the soluble HVEM (sHVEM) was determined in the serum of 36 patients with breast cancer, 50 patients with colorectal cancer and 59 patients with gastric cancer using ELISA method. Moreover, 50 healthy donors (HD) as well as 31 patients with non-ulcer dyspepsia (NUD) were used as control groups. The patients' samples were obtained from the Biobank of Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Results: The level of sHVEM was significantly higher in patients with gastric (P=0.001) and breast cancer (P=0.01) than in control groups (HD). The higher level of sHVEM was observed in colorectal cancer patients in comparison with HD group, although it was not significant. Moreover, the elevated level of sHVEM was shown to be higher significantly in stage III and IV compared to stage I and II in breast cancer (P=0.03). Similar finding was detected in gastric and colorectal cancers, but not to be statistically significant. Conclusion: The results of the present study suggest that the serum level of sHVEM may be considered as a promising indicator for diagnosis as well as evaluating the progression of cancers such as gastric, breast and colorectal cancers.

The rs2302685 polymorphism in the LRP6 gene is associated with bone mineral density and body composition in Iranian children.

BACKGROUND: Some 60-80% of the variability in bone mineral density (BMD) is determined by genetic factors. In the present study, we investigated the impact of the rs2302685 polymorphism of LRP6 on BMD and body composition in Iranian children. METHODS: In total, 200 children (101 boys and 99 girls) were enrolled in the study. Body composition and BMD were computed using the Hologic DXA System (Hologic, Marlborough, MA, USA). The single nucleotide polymorphism of LRP6 rs2302685 (V1062I) was determined using a polymerase chain reaction/restriction fragment length polymorphism. A generalized linear model was performed to find the association between LRP6 polymorphisms, BMD and body composition in two adjusted models. RESULTS: In model 1, a significant difference was found between LRP6 (rs2302685) polymorphism, trochanteric BMD (p = 0.007), intertrochanteric BMD (p = 0.007), total fat (p = 0.001), total fat (%) (p = 0.034), total lean mass (p = 0.031), total Lean + BMC (p = 0.036) and total mass (p = 0.001). In model 2, LRP6 (rs2302685) polymorphisms showed a significant effect on the trochanteric BMD (p = 0.005), intertrochanteric BMD (p = 0.005), total fat (p = 0.001), total fat (%) (p = 0.013) and total mass (p = 0.01). Total fat, total fat (%) and total body mass were higher in subjects with the CC genotype compared to the TT/CT genotype, whereas total lean mass and total Lean + BMC were higher in the TT/CT genotype. CONCLUSIONS: The present study shows that the LRP6 polymorphism may be associated with body composition and BMD in Iranian children.

Influence of Estrogen Receptor Alpha Polymorphism on Bone Mineral Density in Iranian Children.

BACKGROUND: Bone mass acquisition in childhood is directly linked to adult bone mineral density (BMD) and fracture risk. BMD is a heritable trait, more than 70% of its variability among a population is affected by genetic factors. OBJECTIVES: In the present study, we wanted to investigate the association between estrogen receptor alpha (ESR1) polymorphisms, PvuII (rs2234693) and XbaI (rs9340799), and bone area, bone mineral content (BMC), and BMD of the lumbar spine, femoral neck, and also of the total body less the head in Iranian children. METHODS: The ESR1 gene PvuII and XbaI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Bone area, BMC, BMD, and bone mineral apparent density (BMAD) were assessed by dual-energy X-ray absorptiometry (DEXA). Linear regression was carried out to examine the effects of the ESR1 (PvuII and XbaI) polymorphisms on DEXA outputs when adjusted for confounding factors (i.e., age, sex, BMI, and pubertal stage) in 3 models. RESULTS: ESR1 (PvuII) gene polymorphisms (CT vs. CC) showed significant effects on the BMC of the total body less the head in all 3 models. For ESR1 (XbaI), individuals with the AG genotype had higher lumbar spine BMD and lumbar spine BMAD compared to other genotypes. CONCLUSIONS: It seems that the PvuII and XbaI polymorphisms of ESR1 could be associated with BMC and BMD variation in Iranian children and adolescents.

The association of LRP6 rs2302685 (V1062I) polymorphism with the risk of hyperlipidemia in Iranian children and adolescents.

Wnt signaling/LRP6 plays a critical role in metabolic syndrome and atherosclerosis, and variation in this pathway may lead to hyperlipidemia, nonalcoholic fatty liver disease, and coronary artery disease. In the present study, we investigated the effect of LRP6 rs2302685 (V1062I) on hyperlipidemia in Iranian children and adolescents. The population in this study consisted of 200 children (101 boys, 99 girls) aged 9-18 years old. Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL cholesterol, and triglyceride levels were measured. Body composition was evaluated by the Hologic DXA system. PCR/restriction fragment length polymorphism was performed for LRP6 rs2302685 (V1062I) genotyping. Logistic regression analysis was done to find the association between LRP6 rs2302685 (V1062I) and categorized lipid parameters in the adjusted model for confounding factors (age, sex, and puberty). Individuals with the CC genotype showed significantly higher levels of cholesterol, triglycerides, LDL, and non-HDL compared to the CT and TT genotypes. In modeling analysis, for categorized lipid parameters, a significant association was found between CC versus CT, and CC versus TT in terms of cholesterol, LDL, and non-HDL. It seems that LRP6 rs2302685 (V1062I) variant carriers are associated with an increased risk of hyperlipidemia in Iranian children and adolescents.

Association of Nucleotide-binding Oligomerization Domain Receptors with Peptic Ulcer and Gastric Cancer.

Host innate immunity can affect the clinical outcomes of Helicobacter pylori infection, including gastritis, gastric ulcer, gastric adenocarcinoma, and MALT lymphoma. Nucleotide binding oligomerization domain (NOD)-1 and -2 are two molecules of innate immunity which are involved in the host defense against H. pylori. This study aimed to evaluate the effect of the expression level of NOD1 and NOD2 on the susceptibility to gastric cancer as well as peptic ulcer in individuals with H. pylori infection. The gene expression levels of these molecules were compared in three groups of non-ulcer dyspepsia (NUD) as a control group (n=52); peptic ulcer disease (PUD), (n=53); and gastric cancer (GC), (n=39). Relative expression levels of NOD1 in patients with GC were higher than those of NUD and PUD (p<0.001 and P<0.001, respectively). Similarly in case of NOD1, PUD group showed higher level of expression than NUD group (p<0.01). However, there was no significant difference between H. pylori -positive and -negative patients in NUD, PUD, or GC groups. Moreover, the expression levels of NOD2 showed no significant difference among NUD, PUD, or GC groups, while among H. pylori-positive patients, it was higher in GC group than NUD  and PUD groups (p<0.05 and p<0.01, respectively). In addition, positive correlation coefficients were attained between NOD1 and NOD2 expressions in patients with NUD (R2 Linear=0.349, p<0.001), PUD (R2 Linear=0.695, p<0.001), and GC (R2 Linear=0.385, p<0.001). Collectively, the results suggest that the chronic activation of NOD1 and NOD2 receptors might play a role in the development of gastric cancer.