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Inducible nitric oxide synthase 2 promoter polymorphism and malaria disease severity in children in Southern Ghana.

ABSTRACT: OBJECTIVE:We assessed the association of mutant allele frequencies of nitric oxide synthase 2 (NOS2) gene at two SNPs (-954 and -1173) with malaria disease severity in children from a malaria endemic area in Southern Ghana. METHOD:Using children recruited at the hospital, assigned into clinical subgroups of uncomplicated and severe malaria and matching with their "healthy control" counterparts, we designed a case control study. Genomic DNA was extracted and genotyping using Restriction Fragment Polymorphism was done. RESULT:A total of 123 malaria cases (91 uncomplicated, 32 severe) and 100 controls were sampled. Their corresponding mean Hbs were 9.6, 9.3 and 11.2g/dl and geometric mean parasite densities of 32097, 193252 and 0 parasites/ml respectively. Variant allele frequencies varied from 0.09 through 0.03 to 0.12 for G-954C and 0.06 through 0.03 to 0.07 for C-1173T in the uncomplicated, severe and healthy control groups respectively. There was a strong linkage disequilibrium between the two alleles (p<0.001). For the -954 position, the odds of developing severe malaria was found to be 2.5 times lower with the carriage of a C allele compared to those without severe malaria (?2; p< 0.05) though this isn't the case with -1173. CONCLUSION:The carriage of a mutant allele in the -954 NOS2 gene may have a protective effect on malaria among Southern Ghanaian children.

SUBMITTER: Dzodzomenyo M

PROVIDER: S-EPMC6097674 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Inducible nitric oxide synthase 2 promoter polymorphism and malaria disease severity in children in Southern Ghana.

Dzodzomenyo Mawuli M Ghansah Anita A Ensaw Nana N Dovie Benjamin B Bimi Langbong L Quansah Reginald R Gyan Ben A BA Gyakobo Mawuli M Amoani Benjamin B

PloS one 20180817 8

<h4>Objective</h4>We assessed the association of mutant allele frequencies of nitric oxide synthase 2 (NOS2) gene at two SNPs (-954 and -1173) with malaria disease severity in children from a malaria endemic area in Southern Ghana.<h4>Method</h4>Using children recruited at the hospital, assigned into clinical subgroups of uncomplicated and severe malaria and matching with their "healthy control" counterparts, we designed a case control study. Genomic DNA was extracted and genotyping using Restri ...[more]

PMID: 30118498

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Project description:BACKGROUND:Exhaled nitric oxide (FeNO), a biomarker of airway inflammation, predicts asthma risk in children. We previously found that the promoter haplotypes in inducible nitric oxide synthase (NOS2) and exposure to residential traffic independently influence FeNO level. Because NOS2 is inducible by environmental exposures such as traffic-related exposure, we tested the hypothesis that common NOS2 promoter haplotypes modulate the relationship between residential traffic-related exposure and FeNO level in children. METHODS:In a cross-sectional population-based study, subjects (N = 2,457; 7-11 year-old) were Hispanic and non-Hispanic white children who participated in the Southern California Children's Health Study and had FeNO measurements. For residential traffic, lengths of local roads within circular buffers (50m, 100m and 200m radii around homes) around the subjects' homes were estimated using geographic information system (GIS) methods. We interrogated the two most common NOS2 promoter haplotypes that were found to affect FeNO level. RESULTS:The relationship between local road lengths within 100m and 200m circular buffers and FeNO level varied significantly by one of the NOS2 promoter haplotypes (P-values for interaction between road length and NOS2 promoter haplotype = 0.02 and 0.03, respectively). In children who had ?250m of local road lengths within 100m buffer around their homes, those with two copies of the haplotype had significantly lower FeNO (adjusted geometric mean = 11.74ppb; 95% confidence intervals (CI): 9.99 to 13.80) than those with no copies (adjusted geometric mean = 15.28ppb; 95% CI: 14.04 to 16.63) with statistically significant trend of lower FeNO level with increasing number of haplotype copy (P-value for trend = 0.002). In contrast, among children who had >250m of local road lengths within 100m buffer, FeNO level did not significantly differ by the haplotype copy-number (P-value for trend = 0.34). Similar interactive effects of this haplotype and local road lengths within 200m buffer on FeNO were also observed. CONCLUSIONS:Higher exposure from residential traffic nullifies the protective effect of one common NOS2 promoter haplotype on FeNO level. Regulation of traffic-related pollution may protect children's respiratory health.

Project description:AIM:To investigate the role of endothelial nitric oxide synthase -786T > C promoter polymorphism in the etiology of gastric cancer (GC). METHODS:A total of 150 GC patients and 150 control subjects were included in the study. The information on demographic features was elicited with an informed consent from all the patients and control subjects using a structured questionnaire. Helicobacter pylori (H. pylori) infectivity status was tested in antral biopsies from all the subjects by rapid urease test following the method of Vaira et al. Genomic DNA was isolated from whole blood samples following the salting out method of Lahiri et al. Genotype analysis of the rs2070744 polymorphism was carried out by allele-specific polymerase chain reaction method. The genotypes were determined based on the appearance of bands on an agarose gel stained with ethidium bromide under ultraviolet gel documentation with the help of 100 bp ladder. Odds ratios and corresponding 95%CIs were determined using java stat online software. RESULTS:There was a significant difference in the distribution of C allele (C vs T; P = 0.000, OR = 5.038) in patient group compared to the control subjects exhibiting a fivefold increased risk for GC. When the T/T and C/C genotypes were compared, there was an enhanced GC risk for individuals with C/C genotype (T/T vs C/C; P = 0.000). Among the demographic factors, smoking and alcoholism were the common risk factors in patients compared to the control subjects (P < 0.05). Patients with smoking and alcoholism developed cancer even in heterozygous T/C condition (smoking: P = 0.020 and alcoholism: P = 0.005). Individuals with H. pylori infection showed seven fold increased risk for cancer. All the patients with C/C genotype revealed a significant association between H. pylori infection and GC. Among the patients 2.4% of them revealed familial incidence of GC. No significant difference was noticed between cases and controls with regard to consanguinity (P = 0.473). CONCLUSION:The Present data suggest that eNOS-786 C/C genotype and C allele may be considered as potential risk factors in patients with GC.

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Inducible nitric oxide synthase 2 promoter polymorphism and malaria disease severity in children in Southern Ghana.

Publications

Inducible nitric oxide synthase 2 promoter polymorphism and malaria disease severity in children in Southern Ghana.

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