title: Genetic study of two single nucleotide polymorphisms within corresponding microRNAs and susceptibility to tuberculosis in a Chinese Tibetan and Han population.
abstract: MicroRNAs (miRNA) are thought to play important roles in the pathogenesis of diseases. Single nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics via altering their target selection and/or expression, resulting in functional and/or phenotypic changes. We decided to investigate the genetic association with pulmonary tuberculosis with 2 nucleotide variations within corresponding microRNAs regulating the Toll-like receptor (TLR)-mediating signal pathway. MiRNAs potentially regulating the TLR-mediating signal pathway were predicted via bioinformatics. Finally, 2 SNPs, rs2910164 G>C and rs3746444 T>C within miR-146a and miR-499, were selected as candidates in accordance with some criteria. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism and validated by sequencing to demonstrate their association with susceptibility to pulmonary tuberculosis (PTB) in 337 PTB cases and 738 healthy controls, including 318 Tibetan and 757 Han individuals. Bioinformatics databases were searched to support the association between miRNAs and PTB. There was no association between rs3746444 and PTB risk (p = 0.118) in the Han population, but subjects carrying the C allele exhibited decreased PTB risk (odds ratio [OR] = 0.403 [95% confidence interval (95% CI) 0.278-0.583]). However, there was an association between rs3746444 and PTB in the Tibetan population, and individuals carrying the C allele exhibited increased PTB risk (OR = 1.870 [95% CI 1.218-2.871]). A polymorphism (rs2910164 G>C) indicated an association with PTB risk in both Tibetan (p = 0.031) and Han (p = 0.000) populations. However, the role of the G allele of rs2910164, like the C allele in rs3746444, differed in the Tibetan (OR = 1.509, p < 0.05) and Han (OR = 0.575, p < 0.05) groups. This is the first report to suggest that a genetic association with pulmonary tuberculosis with SNPs within the corresponding miRNAs potentially regulates the TLR signal pathway. It is interesting that both the G allele (rs2910164) and the C allele (rs3746444) play different roles in 2 populations. Further functional analysis of the SNP and its impact on mRNA targets is required to confirm the relationship between genotype and phenotype.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Li
authors.forename: Dingdong
authors.initials: D
authors.lastname: Li
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.forename: Xingbo
authors.initials: X
authors.lastname: Song
authors.forename: MeiLang
authors.initials: M
authors.lastname: Qucuo
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Junlong
authors.initials: J
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Binwu
authors.initials: B
authors.lastname: Ying
authors.forename: Chuanmin
authors.initials: C
authors.lastname: Tao
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014376:Tuberculosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D035683:MicroRNAs