Tumour necrosis factor allele variants and their association with the occurrence and severity of malaria in African children: a longitudinal study
Gichohi-Wainaina, W.N. ; Boonstra, A. ; Feskens, E.J.M. ; Demir, A.Y. ; Veenemans, J. ; Verhoef, H. - \ 2015
Malaria Journal 14 (2015). - ISSN 1475-2875 - 11 p.
plasmodium-falciparum malaria - tnf-alpha promoter - cerebral malaria - linkage disequilibrium - rheumatoid-arthritis - diabetes-mellitus - polymorphisms - gene - disease - hla
Background Tumour necrosis factor (TNF) is central to the immune response to Plasmodium infection. Its plasma concentration is influenced by allele variants in the promoter region of TNF. The study’s objectives were to assess TNF allele variants (TNF-1031 , TNF-308 ): (1) modulation of malaria rates in young Tanzanian children; (2) modulation of the severity of malaria as indicated by haemoglobin concentrations at the time of presentation with febrile episodes; and (3) the association between Plasmodium infection and haemoglobin concentration in symptomless parasite carriers. Methods Data from a placebo-controlled trial in which 612 Tanzanian children aged 6–60 months with height-for-age z-score in the range -3 SD to 1.5 SD was utilised. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. An episode of malaria was predefined as current Plasmodium infection with an inflammatory response (axillary temperature =37.5°C or whole blood C-reactive protein concentration =8 mg/L) in children reported sick. Linkage disequilibrium (LD) pattern assessment as well as haplotype analysis was conducted using HAPLOVIEW. Cox regression models used in the primary analysis accounted for multiple episodes per child. Results Genotyping of 94.9% (581/612) children for TNF-1031 (TNF-1031 T>C); allele frequency was 0.39. Corresponding values for rs1800629 (TNF-308 G>A) were 95.4% (584/612) and 0.17. Compared to the wild type genotype (TT), malaria rates were increased in the TNF-1031 CC genotype (hazard ratio, HR [95% CI]: 1.41 [1.01¿1.97] and 1.31 [0.97¿1.76] for crude analysis and adjusting for pre-specified baseline factors, respectively) but decreased in those with the TNF-308 AA genotype (corresponding HR: 0.13 [0.02¿0.63] and 0.16 [0.04¿0.67]). These associations were weaker when analysing first episodes of malaria (P value -0.59 and 0.38, respectively). No evidence that allele variants of TNF-1031 and TNF-308 affected haemoglobin concentration at first episode of malaria, or that they modified the association between Plasmodium infection and haemoglobin concentrations at baseline was observed.
The Tip of the ‘‘Celiac Iceberg’’ in China: A Systematic Review and meta-Analysis
Yuan, J. ; Gao, J. ; Li, Xin ; Liu, F. ; Wijmenga, C. ; Chen, H. ; Gilissen, L.J.W.J. - \ 2013
PLoS ONE 8 (2013)12. - ISSN 1932-6203 - 14 p.
gene-frequencies - disease - wheat - prevalence - hla - populations - patient - people - risk
Methods - By searching the MEDLINE database and four Chinese full-text databases (CNKI, CBM, VIP and WANFANG) (up to August 2012), as well as two HLA allele frequency net databases and the Chinese Statistics Yearbook databases, we systematically reviewed the literature on definite and suspected cases of celiac disease, the predisposing HLA allele frequencies, and on gluten exposure in China. Meta-analysis was performed by analyzing DQ2, DQ8 and DQB1*0201 gene frequencies and heterogeneity in populations from different geographic regions and ethnicities in China. Results - At present, the number of reported celiac disease cases is extremely low in China. The frequencies of the HLA-DQ2.5 and HLA-DQ8 haplotypes were 3.4% (95% confidence interval 1.3–5.5%) and 2.1% (0.1–4.1%), respectively. HLA-DQ2 and HLA-DQ8 antigen frequencies were 18.4% (15.0–21.7%) and 8.0% (4.5–11.4%), respectively. The frequency of the DQB1*0201 allele was 10.5% (9.3–11.6%) and it was more common in the northern Chinese than in the southern Chinese populations. The chance of being exposed to gluten is rapidly increasing all over China nowadays. Conclusion - The data on HLA haplotyping, in conjunction with increasing wheat consumption, strongly suggests that the occurrence of celiac disease is more common in China than currently reported. Coordinated measures by the Chinese government, medical and agricultural research institutions, and food industries, would be justified to create more awareness about celiac disease and to prevent it becoming a medical and societal burden.