INTRODUCTIONInterleukin-18 (IL-18) is a Th1 cytokine, which is postulated to play a role in systemic lupus erythematosus (SLE). Two single nucleotide polymorphisms (SNPs) in the IL-18 promoter gene region were found to influence the quantitative expression of the IL-18 protein. The aim of this study was to determine whether IL-18 promoter gene polymorphisms are associated with SLE.

MATERIALS AND METHODSOne hundred and thirteen Chinese SLE patients and 218 Chinese healthy individuals were recruited. Genomic DNA was extracted from peripheral venous blood. Sequence-specific primer PCR and restriction fragment length polymorphism (RFLP) analysis were used to genotype the DNA samples for SNP-137 and SNP- 607. The following genotypes were obtained: SNP(-607) AA, AC, CC and SNP(-137) GG, GC, CC. Plasma IL-18 concentrations of patients and control subjects were measured by enzyme-linked immunosorbent assay.

RESULTSthe frequency of SNP-607/CC genotype was significantly higher in SLE patients (Pc < 0.05) while genotype SNP-607/AC was significantly decreased in SLE patients compared to the control group (Pc <0.05). Plasma IL-18 concentrations were significantly higher in SLE patients than in control subjects (P <0.05). Both patients and control subjects with CC and AC genotypes have significantly higher IL-18 concentrations than those with AA genotype.

CONCLUSIONThe IL-18 promoter gene polymorphism SNP-607 C allele is associated with SLE and may result in the enhanced production of IL-18 protein in SLE and normal individuals.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Interleukin-18 ; genetics ; Lupus Erythematosus, Systemic ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide

BACKGROUND: Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice. METHODS: Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method. RESULTS: The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice. CONCLUSIONS These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.
Animals ; Arsenic/toxicity* ; Arsenites/toxicity* ; Behavior, Animal/drug effects* ; Environmental Pollutants/toxicity* ; Female ; Gene Expression/drug effects* ; Genetic Markers ; Male ; Maternal Exposure/adverse effects* ; Mice ; Mice, Inbred C3H ; Oxidative Stress/genetics* ; Prefrontal Cortex/drug effects* ; Pregnancy ; Prenatal Exposure Delayed Effects/psychology* ; Reverse Transcriptase Polymerase Chain Reaction ; Serotonin/metabolism* ; Social Behavior ; Sodium Compounds/toxicity*

There has been significant magnitude of problems of diabetes in Myanmar, according to the estimates of International Diabetes Federation (IDF) and the recent National Survey on the prevalence of diabetes. There has been a wide gap of equity between the urban and rural healthcare delivery for diabetes. Myanmar Diabetes Care Model (MMDCM) aims to deliver equitable diabetes care throughout the country, to stem the tide of rising burden of diabetes and also to facilitate to achieve the targets of the Global Action Plan for the Prevention and Control of NCDs (2013-2020). It is aimed to deliver standard of care for diabetes through the health system strengthening at all level. MMDCM was developed based on the available health system, resources and the country's need. Implementation for the model was also discussed.