Association analysis of susceptibility candidate region on chromosome 5q31 for tuberculosis.
Chromosome 5q31 spans the T helper (Th) 2-related cytokine gene cluster, which is potentially important in Th1/Th2 immune responses. The chromosome 5q23.2-31.3 has been recently identified as a region with suggestive evidence of linkage to tuberculosis in the Asian population. With the aim of fine-mapping a putative tuberculosis susceptibility locus, we investigated a family-based association test between the dense single nucleotide polymorphism (SNP) markers within chromosome 5q31 and tuberculosis in 205 Thai trio families. Of these, 75 SNPs located within candidate genes covering SLC22A4, SLC22A5, IRF1, IL5, RAD50, IL13, IL4, KIF3A and SEPT8 were genotyped using the DigiTag2 assay. Association analysis revealed the most significant association with tuberculosis in haplotypes comprising SNPs rs274559, rs274554 and rs274553 of SLC22A5 gene (P(Global)=2.02 x 10(-6)), which remained significant after multiple testing correction. In addition, two haplotypes within the SLC22A4 and KIF3A region were associated with tuberculosis. Haplotypes of SLC22A5 were significantly associated with the expression levels of RAD50 and IL13. The results show that the variants carried by the haplotypes of SLC22A4, SLC22A5 and KIF3A region potentially contribute to tuberculosis susceptibility among the Thai population.
Ridruechai
C
C
Department of Microbiology and Immunology, Mahidol University, Bangkok, Thailand.
Mahasirimongkol
S
S
Phromjai
J
J
Yanai
H
H
Nishida
N
N
Matsushita
I
I
Ohashi
J
J
Yamada
N
N
Moolphate
S
S
Summanapan
S
S
Chuchottaworn
C
C
Manosuthi
W
W
Kantipong
P
P
Kanitvittaya
S
S
Sawanpanyalert
P
P
Keicho
N
N
Khusmith
S
S
Tokunaga
K
K
D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D013785:Thailand; D014376:Tuberculosis / Q000235:genetics*
C087415:KIF3A protein, human; D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D016547:Kinesins