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.
Subject(s)
Chromosomes, Human, Pair 6/genetics , Genetic Predisposition to Disease/genetics , Minisatellite Repeats/genetics , Molecular Chaperones/genetics , Osteoarthritis, Hip/genetics , Osteoarthritis, Knee/genetics , Polymorphism, Single Nucleotide/genetics , Proteins/genetics , Adult , Aged , Aged, 80 and over , Alleles , Case-Control Studies , Croatia , Exons/genetics , Female , Gene Frequency/genetics , Genotype , Humans , Male , Middle Aged , Polymorphism, Genetic/genetics , Polynucleotide Adenylyltransferase , Sex FactorsABSTRACT
Among the predisposing factors to osteoarthritis (OA), a frequent destructive joint disease, is the complex genetic heritage including the interleukin-1 family members like the IL1ß (IL1B) and the IL1 receptor antagonist (IL1RN) genes. The aim of this study was to investigate allelic and genotypic frequencies of the IL1B gene single nucleotide polymorphism (SNP) at -511(G>A) and the variable number tandem repeat (VNTR) in the IL1RN gene in a Croatian Caucasian population of hip OA (HOA) cases and healthy controls. A total of 259 HOA patients with total hip replacement (THR) and 518 healthy blood donors as controls were genotyped for IL1B gene SNP -511(G>A) and the VNTR in the IL1RN gene associated with HOA. The genotype G/A (1/2) at IL1B was significantly associated with the protection of the HOA (p < 0.036, OR = 0.72, 95% CI = 0.52-0.99). The genotype G/G (1/1) had only a trend towards the susceptibility (p = 0.053, OR = 1.35, 95% CI = 0.98-1.86) to disease. None of the haplotypes IL1B -511(G>A) and IL1RN (VNTR) were found associated with the HOA. The haplotype 1-2 at these loci had only a trend to susceptibility (p = 0.065). Haplotype 1-3 had a significant male bias in diseased. Furthermore, genotype comprising 2-1/2-2 haplotypes was found significantly associated with predisposition to HOA (p = 0.027, OR = 2.23, 95% CI = 1.03-4.88), whereas genotype 1-1/2-2 with protection to disease (p = 0.028, OR = 0.65, 95% CI = 0.43-0.97). Our findings suggest that HOA in Croatian population might have a different genetic risk regarding the IL1 locus than has been reported for other Caucasian populations previously.
Subject(s)
Interleukin 1 Receptor Antagonist Protein/genetics , Interleukin-1beta/genetics , Osteoarthritis, Hip/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Croatia , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Minisatellite Repeats , Osteoarthritis, Hip/surgery , Polymorphism, Single Nucleotide , White People , Young AdultABSTRACT
BACKGROUND: Genetic susceptibility to cancer is multifactorial, and it is known that impairment of the immune system could contribute to risk for getting cancer. AIM OF THE STUDY: Single-nucleotide polymorphisms (SNPs) of Toll-like receptor (TLR) 2, TLR3, TLR4, and TLR9 genes, which are important for innate immunity, were analyzed for the association with breast cancer. METHODS: The SNPs comprised TLR2 (c.597T>C), TLR2 (c.1350T>C), TLR3 (c.1377C>T), TLR4 (c.896A>G), and TLR9 (c.1635A>G). The allelic and genotypic frequencies of these TLR SNPs were compared between patients (n = 130) and controls (n = 101) in a case-control study from Croatia. RESULTS: TLR SNPs were not significantly different. From the population genetics viewpoint, we found that a hypomorphic variant of TLR4 (p.Asp299Gly) allele has no specific allelic frequency (8.4%) in the Croatian population (n = 496) compared to other Caucasians (6.5-10%). CONCLUSION: These results suggest that polymorphisms in tested TLR genes are not likely to be associated with increased risk for developing breast cancer.
Subject(s)
Breast Neoplasms/genetics , Genetic Predisposition to Disease , Immunity, Innate/genetics , Polymorphism, Single Nucleotide , Toll-Like Receptors/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Middle Aged , Toll-Like Receptor 2/genetics , Toll-Like Receptor 3/genetics , Toll-Like Receptor 4/genetics , Toll-Like Receptor 9/geneticsABSTRACT
OBJECTIVE: In search for possible novel genes that may be involved in tooth development, we analysed the genome-wide transcriptome of developing mandibular tooth germs of mouse during embryonic and early life and selected family-with-sequence-similarity-46, member A (Fam46a) gene for further expression analysis. METHODS: We applied microarray, quantitative real time polymerase chain reaction and in situ hybridisation methods for the expression study of the mouse Fam46a gene. RESULTS: We found the family-with-sequence-similarity-46, member A (Fam46a) gene to be highly expressed and further verify its temporo-spatial expression in the mouse tooth. CONCLUSION: We have shown that Fam46a is expressed in ameloblasts' nuclei of tooth germs and hypothesise that it might act together with morphogenetic factors important for the formation of enamel in mouse tooth.
Subject(s)
Amelogenesis/genetics , Proteins/genetics , Tooth Germ/embryology , Ameloblasts/metabolism , Animals , Gene Expression , Gene Expression Regulation, Developmental , In Situ Hybridization , Mice , Mice, Inbred Strains , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction , Tooth Germ/growth & developmentABSTRACT
We have developed a dual probe quantitative PCR (qPCR) mini array enabling a more accurate analysis of the relationship between copy number variants (CNVs) and other genomic features in specific areas. We used it to map hemizygous microdeletion on human chromosome 7 around the elastin gene (ELN), which is the molecular basis of the Williams-Beuren syndrome (WBS). In two WBS patients, the haploid content of the elastin gene was ascertained previously by the fluorescence in-situ hybridization (FISH). Our dual-color qPCR assay used this information to normalize for DNA content in all tests. We mapped the extent of the deleted area using 10 loci spanning over 4 Mb. A border region containing the GTF2I gene, usually deleted in most cases, was found about 10 times amplified in both patients, suggesting an unusual type of the WBS genetic defect. This 10-WBS-loci-specific qPCR assay could be an affirmative diagnostic tool alternative to FISH. Due to low cost, it could be used as a screening test that would not only facilitate research on CNVs, but also allow early diagnosis of the disease, as well-timed diagnosis would benefit WBS children with earlier proper health-care measures.
