Uridine diphospho-glucuronosyltransferase 1 (UGT1A1) is involved in estradiol glucuronidation, which may play a central role in the etiology of breast cancer. A common insertion/deletion polymorphism ...in the TATAA-box of the promoter region of UGT1A1 results in decreased initiation of transcription, and has been associated with breast cancer risk in different ethnic groups. In the present study, the role of the above genetic variation at the UGT1A1 locus in breast cancer susceptibility was investigated in a homogeneous population. Our case-control study included 136 women with breast cancer and 186 healthy female controls of Greek origin. The polymorphism A(TA)nTAA in the promoter region of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7, and normal homozygous 6/6) were identified. No significant associations were observed between the 7/7 genotype and breast cancer risk, indicating that further studies in Caucasian women are needed to elucidate the role of UGT1A1 polymorphism in breast cancer risk.
The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis. In the discovery study, the Rotterdam Study-I, 7 single nucleotide ...polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls. The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (alpha = 0.05). This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The association between cytokine gene polymorphisms and chronic osteomyelitis was investigated in order to determine whether genetic variability in cytokine genes predisposes to osteomyelitis ...susceptibility. Significant genotypic and allelic associations were observed between interleukin 1alpha (IL-1alpha) -889-C/T, IL-4 -1098-G/T and -590-C/T, and IL-6 -174-G/C polymorphisms and osteomyelitis in the Greek population, pointing towards their potential involvement in osteomyelitis pathogenesis.
Objective
To identify novel genes involved in osteoarthritis (OA), by means of a genome‐wide association study.
Methods
We tested 500,510 single‐nucleotide polymorphisms (SNPs) in 1,341 Dutch ...Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and ∼39,000 controls. Meta‐analyses were performed using the program Comprehensive Meta‐analysis, with P values <1 × 10−7 considered genome‐wide significant.
Results
The C allele of rs3815148 on chromosome 7q22 (minor allele frequency 23%; intron 12 of the COG5 gene) was associated with a 1.14‐fold increased risk (95% confidence interval 1.09–1.19) of knee and/or hand OA (P = 8 × 10−8) and also with a 30% increased risk of knee OA progression (95% confidence interval 1.03–1.64) (P = 0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (68 kb upstream of GPR22), which is associated with GPR22 expression levels in lymphoblast cell lines (P = 4 × 10−12). Immunohistochemistry experiments revealed that G protein–coupled receptor protein 22 (GPR22) was absent in normal mouse articular cartilage or synovium. However, GPR22‐positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged with in vivo papain treatment or methylated bovine serum albumin treatment. GPR22‐positive chondrocyte‐like cells were also found in osteophytes in instability‐induced OA.
Conclusion
Our findings identify a novel common variant on chromosome 7q22 that influences susceptibility to prevalence and progression of OA. Since the GPR22 gene encodes a G protein–coupled receptor, this is potentially an interesting therapeutic target.
Causes of chromosomal nondisjunction is one of the remaining unanswered questions in human genetics. In order to increase our understanding of the mechanisms underlying nondisjunction we have ...performed a molecular study on trisomy 8 and trisomy 8 mosaicism. We report the results on analyses of 26 probands (and parents) using 19 microsatellite DNA markers mapping along the length of chromosome 8. The 26 cases represented 20 live births, four spontaneous abortions, and two prenatal diagnoses (CVS). The results of the nondisjunction studies show that 20 cases (13 maternal, 7 paternal) were probably due to mitotic (postzygotic) duplication as reduction to homozygosity of all informative markers was observed and as no third allele was ever detected. Only two cases from spontaneous abortions were due to maternal meiotic nondisjunction. In four cases we were not able to detect the extra chromosome due to a low level of mosaicism. These results are in contrast to the common autosomal trisomies (including mosaics), where the majority of cases are due to errors in maternal meiosis.
Objective
GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the ...rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large‐scale meta‐analysis of individual‐level data.
Methods
Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex‐specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed‐effects and random‐effects models for allele‐based effects, and also for haplotype effects for FRZB.
Results
A significant random‐effects summary OR for knee OA was demonstrated for rs143383 (1.15 95% confidence interval 1.09–1.22) (P = 9.4 × 10−7), with no significant between‐study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between‐study heterogeneity was observed, and statistical significance was borderline (for OA of the hip P = 0.016) or absent (for OA of the hand P = 0.19). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P = 0.019).
Conclusion
Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes.
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