title: Genetic factors associated with development of cerebral malaria and fibrotic schistosomiasis.
abstract: Collaborative studies have identified some genetic factors contributing to the development of severe forms of malaria and schistosomiasis. In Thailand, the TNF-alpha 5'-flanking region shows biallelic polymorphic sites at nucleotides -238, -308, -857, -863, and -1031, and seven alleles have been identified in patients from Myanmar. We found that the TNF promoter (TNFP)-D allele was significantly associated with cerebral malaria in populations from Karen (P < 0.0001, OR = 124.86) and ethnic Burma (P < 0.0001, OR = 34.50). In China, we have identified two major genes related to the severity of liver fibrosis, one an HLA class II gene, and the other the IL-13 gene. The frequency of the HLA-DRB5*0101 allele and that of the IL-13 promoter A/A (IL-13P- A/A) genotype were elevated in fibrotic patients, although the two genes are located on different chromosomes, chromosomes 6p and 5q, respectively. Subjects with both genotypes had odds ratios (OR = 24.5) much higher than the sum of the ratios for each individual genotype (OR = 5.1, 95% Confidence Interval 1.3-24.7 for HLA-DRB5*0101, OR = 3.1 95% CI 1.5 - 6.5 for IL-13P- A/A). That the effects of the two susceptibility markers are synergistic rather than additive, strongly suggests that the pathogenic Th2 response directly influences the prognosis of post-schistosomal liver fibrosis.
authors.affiliation: Department of Molecular Immunogenetics, Institute of Tropical Medicine Nagasaki University, Nagasaki, 852-8523, Japan. hiraken@net.nagasaki-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D000483:Alleles; D001208:Asia; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics; D008103:Liver Cirrhosis / Q000235:genetics; D016779:Malaria, Cerebral / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012554:Schistosomiasis japonica / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D005819:Genetic Markers; D006684:HLA-DR Antigens; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha