Common MCL1 polymorphisms associated with risk of tuberculosis.
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.
Shin
Hyoung Doo
HD
Clinical Research Center for Tuberculosis, National Masan Tuberculosis Hospital, Masan, Korea.
Cheong
Hyun Sub
HS
Park
Byung Lae
BL
Kim
Lyoung Hyo
LH
Han
Chang Su
CS
Lee
In Hee
IH
Park
Seung Kyu
SK
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*
D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2