title: Common MCL1 polymorphisms associated with risk of tuberculosis.
abstract: MCL1 expression has been found to be up-regulated during infection with virulent Mycobacterium tuberculosis. We investigated the genetic polymorphisms in MCL1 as potential candidate gene for a host genetic study of clinical TB infection. We have sequenced exons and their boundaries of MCL1, including the 1.5 kb promoter region, to identify polymorphisms, and eight polymorphisms were identified. The genetic associations of polymorphisms in MCL1 with clinical TB patients (n=486) and normal controls (n=370) were analyzed. Using statistical analyses, one common promoter polymorphism (MCL1- 324C > A) which is absolutely linked with three other SNPs in the promoter and 3'UTR regions, were found to be significantly associated with increased risk of clinical TB disease. The frequency of the A-bearing genotype of -324C > A was higher in clinical TB patients than in normal controls (P=0.0008, OR= 1.68). Our findings suggest that polymorphisms in MCL1 might be one of genetic factors for the risk of clinical tuberculosis development.
authors.affiliation: Clinical Research Center for Tuberculosis, National Masan Tuberculosis Hospital, Masan, Korea.
authors.forename: Hyoung Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Cheong
authors.forename: Byung Lae
authors.initials: BL
authors.lastname: Park
authors.forename: Lyoung Hyo
authors.initials: LH
authors.lastname: Kim
authors.forename: Chang Su
authors.initials: CS
authors.lastname: Han
authors.forename: In Hee
authors.initials: IH
authors.lastname: Lee
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D020641:Polymorphism, Single Nucleotide; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000235:genetics*
chemical_list: D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2