title: Association of variable number of tandem repeats in the coding region of the FAM46A gene, FAM46A rs11040 SNP and BAG6 rs3117582 SNP with susceptibility to tuberculosis.
abstract: We analyzed for association between the Family with sequence similarity 46, member A (FAM46A) gene (located on chromosome 6q14.1), BCL2-Associated Athanogene 6 (BAG6) gene (located on chromosome 6p21.3) and tuberculosis in Croatian Caucasian. We genotyped the FAM46A rs11040 SNP, FAM46A VNTR and BAG6 rs3117582 polymorphisms in a case-control study with 257 tuberculosis patients and 493 healthy individuals in a Croatian Caucasian population. We found that genotype FAM46A 3/3 (three VNTR repeats homozygote) was associated with susceptibility to tuberculosis (p<0.0015, Pcorr.<0.029, Odds ratio = 2.42, 95% Confidence Interval = 1.34-4.3). This association suggests that the protein domain encoded by the VNTR might be important for the function of the FAM46A protein, which, in turn, could be relevant in developing tuberculosis. In addition, we found that FAM46A rs11040 SNP:FAM46A VNTR:BAG6 haplotype 132 (G-3-C) is associated with susceptibility to tuberculosis (p<0.012, pcorr.<0.024, Odds ratio 3.45, 95% Confidence Interval = 1.26-9.74). This may suggests that the interaction between the FAM46A and BAG6 proteins may be involved in tuberculosis etiology. We found also that infection of human macrophages with heat-killed M. tuberculosis (H37Rv) led to over-expression of FAM46A (VNTR 3/4) transcript. This is the first study to show associations between the FAM46A gene VNTR polymorphisms, FAM46A rs11040 SNP:FAM46A VNTR:BAG6 haplotypes and any disease.
authors.affiliation: Molecular Genetics Laboratory Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
authors.forename: Godfrey Essien
authors.initials: GE
authors.lastname: Etokebe
authors.affiliation: Section of Pulmology, Department of Internal Medicine, Clinical Hospital Center, University of Rijeka, Rijeka, Croatia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Bulat-Kardum
authors.affiliation: Dept of Immunology, OUS-Rikshospitalet, Oslo, Norway.
authors.forename: Ludvig Andre
authors.initials: LA
authors.lastname: Munthe
authors.affiliation: Clinical Institute for Transfusion Medicine, Universal Hospital Center Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Balen
authors.affiliation: Molecular Genetics Laboratory Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Dembic
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000483:Alleles; D017523:Croatia; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D020641:Polymorphism, Single Nucleotide; D011062:Polynucleotide Adenylyltransferase; D011506:Proteins / Q000235:genetics*; D020080:Tandem Repeat Sequences; D014376:Tuberculosis / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C496515:BAG5 protein, human; D011506:Proteins; D011062:Polynucleotide Adenylyltransferase; C466099:TENT5A protein, human