title: High Incidence of Malaria Along the Sino-Burmese Border Is Associated With Polymorphisms of CR1, IL-1A, IL-4R, IL-4, NOS, and TNF, But Not With G6PD Deficiency.
abstract: Malaria is highly endemic in Yunnan Province, China, with the incidence of malaria being highest along the Sino-Burmese border. The aim of our study was to determine whether genetic polymorphisms are associated with the prevalence of malaria among Chinese residents of the Sino-Burmese border region. Fourteen otherwise healthy people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, 50 malaria patients, and 67 healthy control subjects were included in our cross-sectional study. We analyzed the frequency of the G3093T and T520C single-nucleotide polymorphisms (SNPs) of CR1. Logistic regression was used to calculate the prevalence odds ratio (POR) and 95% confidence interval (CI) of malaria for the T520C SNP of CR1 and SNPs of G6PD, IL-4, IL-4R, IL-1A, NOS, CD40LG, TNF, and LUC7L. The frequency of the 3093T/3093T genotype of CR1 in the malaria group (0.16) was significantly higher than that in the control group (0.045, P < 0.05), and significantly lower than that in the G6PD deficiency group (0.43, P < 0.01). The frequency of the 520T/520T genotype of CR1 was significantly higher in the malaria patients (0.78) than that in the control group (0.67, P < 0.05) and G6PD-deficiency group (0.36, P < 0.05). The T allele of the T520C variant of CR1 was significantly associated with the prevalence of malaria (POR: 1.460; 95% CI: 0.703-3.034). Polymorphisms of G6PD did not significantly influence the prevalence malaria (P > 0.05). A GTGTGTC haplotype consisting of IL-1A (rs17561), IL-4 (rs2243250), TNF (rs1800750), IL-4R (rs1805015), NOS (rs8078340), CD40LG (rs1126535), and LUC7L (rs1211375) was significantly associated with the prevalence of malaria (POR: 1.822, 95% CI: 0.998-3.324). The 3093G/3093G and 520T/520T genotypes are the predominant genetic variants of CR1 among Chinese residents near the Sino-Burmese border, and the T allele of T520C is associated with the prevalence of malaria in this region. Although G6PD deficiency does not protect against malaria, it may diminish the association between malaria and the CR1 polymorphisms in this population. The GTGTGTC haplotype is also associated with the prevalence of malaria in this region.
authors.affiliation: From the Department of Biochemistry and Molecular Biology (NR, LC, C-HZ, Q-LT, Z-QY, Y-SH, Y-CZ); and First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, PR China (Y-MK).
authors.forename: Na
authors.initials: N
authors.lastname: Ren
authors.forename: Ying-Min
authors.initials: YM
authors.lastname: Kuang
authors.forename: Qiong-Lin
authors.initials: QL
authors.lastname: Tang
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Zhang
authors.forename: Zao-Qing
authors.initials: ZQ
authors.lastname: Yang
authors.forename: Yong-Shu
authors.initials: YS
authors.lastname: He
authors.forename: Yue-Chun
authors.initials: YC
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000483:Alleles; D002681:China / Q000453:epidemiology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005838:Genotype; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007378:Interleukins / Q000235:genetics; D008288:Malaria / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D002052:Myanmar / Q000453:epidemiology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D016601:RNA-Binding Proteins / Q000235:genetics*; D017463:Receptors, Complement 3b / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C509991:CR1 protein, human; D016207:Cytokines; D007378:Interleukins; C426524:LUC7L protein, human; D016601:RNA-Binding Proteins; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase