title: Susceptibility to large-joint osteoarthritis (hip and knee) is associated with BAG6 rs3117582 SNP and the VNTR polymorphism in the second exon of the FAM46A gene on chromosome 6.
abstract: Family with sequence similarity 46, member A (FAM46A) gene VNTR and BCL2-Associated Athanogene 6 (BAG6) gene rs3117582 polymorphisms were genotyped in a case-control study with 474 large-joint (hip and knee) osteoarthritis (OA) patients and 568 controls in Croatian population by candidate-gene approach for association with OA. We found that BAG6 rs3117582 SNP genotypes were associated with protection (major allele homozygote) and susceptibility (major-minor allele heterozygote) to OA. BAG6 rs3117582 major allele (A) was associated with reduced risk to OA while the minor allele (C) was associated with increased risk to OA. We identified 6 alleles harboring 2 to 7 repeats making 20 genotypes for FAM46A. A rare FAM46A VNTR genotype comprising VNTR alleles with four and seven repeats (c/f) was associated with increased OA risk in both genders. The genotype with four and six repeats (c/e) was also associated with increased risk to OA in males. A polymorphic FAM46A allele with six repeats (e) was associated with reduced risk to OA in females. Our results suggest association between the FAM46A gene, BAG6 gene and OA in Croatian population, respectively. This is the first study to show associations between these genetic loci and OA.
authors.affiliation: Department of Oral Biology, Molecular Genetics Laboratory, University of Oslo, Oslo, 0316, Norway.
authors.forename: Godfrey E
authors.initials: GE
authors.lastname: Etokebe
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Jotanovic
authors.forename: Radovan
authors.initials: R
authors.lastname: Mihelic
authors.forename: Biserka
authors.initials: B
authors.lastname: Mulac-Jericevic
authors.forename: Tamara
authors.initials: T
authors.lastname: Nikolic
authors.forename: Sanja
authors.initials: S
authors.lastname: Balen
authors.forename: Branko
authors.initials: B
authors.lastname: Sestan
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Dembic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D017523:Croatia; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics*; D015207:Osteoarthritis, Hip / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011062:Polynucleotide Adenylyltransferase; D011506:Proteins / Q000235:genetics*; D012737:Sex Factors
chemical_list: C092009:BAG6 protein, human; D018832:Molecular Chaperones; D011506:Proteins; D011062:Polynucleotide Adenylyltransferase; C466099:TENT5A protein, human
keywords: genetic association; osteoarthritis; single nucleotide polymorphism; variable number of tandem repeats