A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis

2012 ◽  
Vol 71 (5) ◽  
pp. 714-717 ◽  
Author(s):  
Roberto Díaz-Peña ◽  
Ana M Aransay ◽  
Beatriz Suárez-Álvarez ◽  
Jacome Bruges-Armas ◽  
Naiara Rodríguez-Ezpeleta ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
High Throughput ◽  
Human Leucocyte Antigen ◽  
Chromosome Region ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Hla B27 ◽  
Single Nucleotide ◽  
Sliding Windows ◽  
Genomic Variants

ObjectiveTo identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations.MethodsHigh-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive.ResultsTwo markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10−3) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43×10−4 to 6.54×10−4). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73×10−6). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS.ConclusionA novel significant association was detected between SNP rs1055234 and AS susceptibility.

ARTS1 polymorphisms are associated with ankylosing spondylitis in Koreans

2009 ◽  
Vol 69 (3) ◽  
pp. 582-584 ◽  
Author(s):  
Chan-Bum Choi ◽  
Tae-Hwan Kim ◽  
Jae-Bum Jun ◽  
Hye-Soon Lee ◽  
Seung Cheol Shim ◽  
...  
Keyword(s):  
New York ◽  
Ankylosing Spondylitis ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Polymorphisms ◽  
Caucasian Population ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Pathogenetic Mechanisms ◽  
Caucasian Patients

ObjectiveTo test the association between ARTS1 polymorphisms and Koreans with ankylosing spondylitis (AS).MethodsAll patients and controls were Korean. 872 patients with AS fulfilling the modified New York criteria and 403 healthy controls were genotyped for five single nucleotide polymorphisms (SNPs), rs27044, rs17482078, rs10050860, rs30107 and rs2287987, known to be associated with AS in Caucasians.ResultsSNPs rs27044 (p=9.37 × 10−7) and rs30187 (p=7.16 × 10−6) of ARTS1 were significantly associated with AS in Koreans. There was no significant association for rs17482078, rs10050860 and rs2287987. Two four-marker haplotypes were found to be associated with AS (GCCT: p=4.71×10−7, CCCC: p=8.56×10−6).ConclusionsThis is first confirmation in a non-Caucasian population that genetic polymorphisms in ARTS1 are associated with AS, implicating common pathogenetic mechanisms in Korean and Caucasian patients with AS.

IL-23R Polymorphisms in Patients with Ankylosing Spondylitis in Korea: Table 1.

2009 ◽  
Vol 36 (5) ◽  
pp. 1003-1005 ◽  
Author(s):  
IL-HOON SUNG ◽  
TAE-HWAN KIM ◽  
SO-YOUNG BANG ◽  
TAE-JONG KIM ◽  
BITNARA LEE ◽  
...  
Keyword(s):  
New York ◽  
Ankylosing Spondylitis ◽  
Single Nucleotide Polymorphisms ◽  
Gene Cluster ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Korean Patients ◽  
Caucasian Patients

Objective.IL23R polymorphisms have been shown to have a significant association with ankylosing spondylitis (AS). To date, these studies have been restricted to Caucasian patients with AS. Our study addresses this relationship in Korean patients with AS.Methods.A total of 451 patients with AS and 392 ethnically matched healthy controls were enrolled. All patients were native Koreans with AS satisfying the modified New York criteria. In total, 10 single nucleotide polymorphisms (SNP) within the IL-23R gene cluster were genotyped.Results.No IL-23R SNP were found to be associated with AS in Koreans.Conclusion.The association of IL23R and AS that is seen in Caucasian patients with AS is not present in Korean patients with AS.

scholarly journals Association of Interleukin-10 gene polymorphisms with ankylosing spondylitis

2011 ◽  
Vol 34 (6) ◽  
pp. 370 ◽  
Author(s):  
Chengyu Lv ◽  
Yingzheng Wang ◽  
Jinqin Wang ◽  
Haining Zhang ◽  
Hao Xu ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Single Nucleotide Polymorphisms ◽  
Odds Ratio ◽  
Serum Levels ◽  
Interleukin 10 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Snp Analysis ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Objective: Genetic polymorphisms of the Interleukin-10 (IL-10) promoter have been implicated in several autoimmune diseases, including seronegative spondyloarthropathies. This study investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of IL-10 are associated with ankylosing spondylitis (AS), a common subtype of spondyloarthritis (SpA). Methods: The serum levels of IL-10 were measured with an enzyme-linked immunosorbent assay (ELISA). The single nucleotide polymorphisms (SNPs) at positions -1082A/G, -819C/T and -592C/A in the IL-10 gene promoter were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: 110 AS patients and 120 ethnic-matched healthy controls were included in this study. The serum levels of IL-10 were significantly higher in AS patients than healthy controls (Z=-10.9, P < 0.001). Single SNP analysis showed no significant differences in the allelic and genotypic frequencies of -592A/C between the AS patients and healthy controls. No -1082GG genotype was found in this study. An increased frequency of -1082G allele was noted in AS patients (P=0.047). In a logistic regression analysis, the -1082AG genotype was associated with an odds ratio of 1.993 (95%CI, 1.046-3.800, P=0.034) for AS. And the -819CC genotype was associated with an odds ratio of 3.125 (95%CI, 1.246-7.836, P=0.015) for AS. Furthermore, haplotype analysis revealed that GCC haplotype was associated with a significantly increased risk of AS as compared with the ATA haplotype (OR=2.19; 95% CI, 1.13-4.26; P=0.02). Conclusion: Our results indicate that the gene haplotype of IL-10 can contribute to the susceptibility to AS in a Chinese population.

Association ofARTS1Gene Polymorphisms with Ankylosing Spondylitis in the Hungarian Population: The rs27044 Variant Is Associated with HLA-B*2705 Subtype in Hungarian Patients with Ankylosing Spondylitis

2009 ◽  
Vol 37 (2) ◽  
pp. 379-384 ◽  
Author(s):  
BORBÁLA PAZÁR ◽  
ENIKO SÁFRÁNY ◽  
PÉTER GERGELY ◽  
SÁNDOR SZÁNTÓ ◽  
ZOLTÁN SZEKANECZ ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Hla B27 ◽  
Allelic Discrimination ◽  
Single Nucleotide ◽  
Predominant Subtype ◽  
Hungarian Population ◽  
Polymerase Chain ◽  
Control Study

Objective.Associations have been found between ankylosing spondylitis (AS) and polymorphisms in the aminopeptidase regulator of TNFR1 shedding (ARTS1) gene. We studied the association of 5 polymorphisms within theARTS1gene with AS in Hungarian patients. We also investigated the prevalence of HLA-B27 subtypes in the Hungarian population.Methods.A case-control study including 297 patients with AS and 200 sex and ethnically matched healthy controls was performed. Patients and controls were genotyped for rs27044, rs17482078, rs10050860, rs30187, and rs2287987 single-nucleotide polymorphisms using real-time polymerase chain reaction (PCR) allelic discrimination. HLA-B27 subtypes were determined with PCR sequence-specific primer (PCR-SSP) technique.Results.We observed a significant increase in the minor allele frequency of rs27044 (p = 0.001) in the AS group compared to controls. The minor allele frequencies of rs10050860 (p = 0.006) and rs2287987 (p = 0.002) showed a significant decrease in AS patients compared to controls. Haplotype analysis revealed association of 2 ARTS1 haplotypes with AS in the Hungarian population. We found that HLA-B*2705 was the predominant subtype in Hungarians with AS. Carriage of the G allele of rs27044 was significantly associated with the HLA-B*2705 subtype (p = 0.009) in AS patients.Conclusion.We confirmed reported associations ofARTS1gene polymorphisms with AS in a Hungarian cohort study. We found HLA-B*2705 as the predominant subtype in Hungarian AS patients in accord with other studies on Caucasian populations. Our results suggest that theARTS1gene variants together with HLA-B27 strongly contribute to disease susceptibility in patients with AS.

Genetic Studies of Ankylosing Spondylitis in Koreans Confirm Associations with ERAP1 and 2p15 Reported in White Patients

2010 ◽  
Vol 38 (2) ◽  
pp. 322-324 ◽  
Author(s):  
SO-YOUNG BANG ◽  
TAE-HWAN KIM ◽  
BITNARA LEE ◽  
EUNJI KWON ◽  
SANG HYUN CHOI ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Gene Desert ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Nonwhite Population ◽  
Endoplasmic Reticulum Aminopeptidase 1 ◽  
Anglo American ◽  
White Patients

Objective.Investigators from the Australo-Anglo-American Spondyloarthritis Consortium have reported additional genes associated with ankylosing spondylitis (AS) susceptibility including IL1R2, ANTXR2, and gene deserts at 2p15 and 21q22. We evaluated these new candidate genes in a large cohort of Korean patients with AS.Methods.A group of 1164 patients with AS and 752 healthy controls were enrolled for our study. Eight single-nucleotide polymorphisms (SNP) were analyzed to define genetic association with AS by MassARRAY system.Results.Significant positive associations of AS with endoplasmic reticulum aminopeptidase 1 SNP, rs27037 (p = 1.31 × 10−4), and rs27434 (p = 4.59 × 10−6), were observed. The rs10865331 of gene desert at 2p15 also showed a significant association with AS (p = 4.63 × 10−5).Conclusion.This is the first confirmation in a nonwhite population that genetic polymorphisms of rs27037, rs27434, and rs10865331 are associated with AS, implicating common pathogenetic mechanisms in Korean and white patients with AS.

scholarly journals Association of Genetic Variants of RANK, RANKL, and OPG with Ankylosing Spondylitis Clinical Features in Taiwanese

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Chin-Man Wang ◽  
Shu-Chun Tsai ◽  
Jing-Chi Lin ◽  
Yeong-Jian Jan Wu ◽  
Jianming Wu ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Chronic Inflammatory Disease ◽  
Nuclear Factor ◽  
Nucleotide Polymorphisms ◽  
Bone Homeostasis ◽  
Hla B27 ◽  
Onset Age ◽  
Single Nucleotide ◽  
Protein Complex Formation ◽  
Receptor Activator

Ankylosing spondylitis (AS) is a chronic inflammatory disease that leads to spinal ankylosis. The receptor activator of the nuclear factor-kappa (RANK), RANK ligand, and osteoprotegerin (OPG) (RANK/RANKL/OPG) pathway plays critical roles in bone metabolism and the immune system. The current study was aimed at investigating whether six single-nucleotide polymorphisms (SNPs) within the RANK, RANKL, and OPG genes essential for bone homeostasis are associated with AS. Genotype distributions, allele and haplotype frequencies, were compared between 1120 AS patients and 1435 healthy controls and among AS patients with stratification by syndesmophyte formation, onset age, and HLA-B27 positivity. We found that RANKL SNPs were associated with AS syndesmophyte formation. Notably, the RANKL SNP haplotype rs7984870C/rs9533155G/rs9525641C was negatively associated with AS susceptibility and appeared to protect against syndesmophyte formation in AS. Functionally, RANKL promoter SNPs (rs9525641 C/T and rs9533155 G/C) affected DNA-protein complex formation and promoter activity in promoter reporter analyses. The OPG SNP haplotype rs2073618G/rs3102735T was significantly associated with HLA-B27 negativity in AS patients. Furthermore, AS patients with syndesmophyte formation had significantly lower levels of soluble RANKL levels than those without syndesmophyte formation. Our data suggested a role for RANKL in AS susceptibility and severity.

scholarly journals Association Study of Single Nucleotide Polymorphisms Rs4552569/Rs17095830 with Ankylosing Spondylitis in A Chinese Population

2016 ◽  
Vol 10 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Qingwen Wang ◽  
Yuanyuan Yang ◽  
Jiyang Lv ◽  
Qi Lin ◽  
Luo Wang ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Han Chinese ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Melting Analysis ◽  
Inflammatory Bowel

Genetics play a key role in ankylosing spondylitis (AS). A previous genome-wide association study (GWAS) showed that rs4552569 (on 5q14.3) and rs17095830 (on 12q12) were associated with the risk of AS in Han Chinese, which was not replicated in other two studies. In the current study, rs4552569 and rs17095830 were genotyped in 735 Han Chinese AS patients and 1204 healthy controls using high resolution melting analysis (HRMA). We compared the distributions of genotypes and alleles between AS cases and healthy controls. Rs30187 and rs10865331, which were reported to be associated with AS susceptibility in various populations, were also genotyped and analyzed as positive controls. The results showed that no association between rs4552569/rs17095830 polymorphisms and AS susceptibility was found. On the other hand, an association between rs17095830 and one of AS complication (inflammatory bowel disease) was observed (allelic P value=0.0180; odds ratio[OR]=1.739; 95% confidence interval [CI]=1.146-2.639).

scholarly journals Association of ERAP1, IL23R and PTGER4 Polymorphisms with Radiographic Severity of Ankylosing Spondylitis

2017 ◽  
Vol 11 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Gulsen Ozen ◽  
Rabia Deniz ◽  
Fatih Eren ◽  
Can Erzik ◽  
Ali Ugur Unal ◽  
...  
Keyword(s):  
New York ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Ankylosing Spondylitis ◽  
Disease Duration ◽  
Smoking Status ◽  
Nucleotide Polymorphisms ◽  
Hla B27 ◽  
Single Nucleotide ◽  
Radiographic Severity

Background: Radiographic severity of ankylosing spondylitis (AS) shows such great variance that some patients never develop syndesmophytes throughout the entire disease span, whereas some develop bamboo spine relatively early. Objective: To study the association between ERAP1, IL23R and PTGER4 single nucleotide polymorphisms (SNPs) and radiographic severity in AS patients. Methods: rs27044 and rs30187 (ERAP1), rs11209032 (IL23R) and rs10440635 (PTGER4) SNPs were genotyped in 235 AS patients fulfilling the modified New York criteria. Patients were classified as mild- and severe-AS according to modified Stoke AS spinal score (mSASSS). Mild-AS is defined as having mSASSS of “0” following at least 10 years of disease duration. Severe-AS is defined as having mSASSS of >20 (patients with mild vertebral changes (i.e. squaring or erosions) were omitted for clear stratification) regardless of disease duration. Results: The genotype distributions and allele frequencies of ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs were similar in mild- (n=171, mSASSS=0, 55.6% HLA-B27 positive) and severe-AS patients (n=64, mSASSS=48.5±17.8, 73.4% HLA-B27 positive). After adjustment for clinical differences between groups (gender, disease duration, HLA-B27 and smoking status) by logistic regression analysis, none of the alleles in the investigated SNPs were found to be associated with radiographic severity of AS. Conclusion: In radiographically well-categorized AS patients, ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs are not found to be associated with radiographic severity of AS.

scholarly journals Prediction of Ankylosing Spondylitis in the HUNT Study by a Genetic Risk Score Combining 110 Single-nucleotide Polymorphisms of Genome-wide Significance

2019 ◽  
Vol 47 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Sina Rostami ◽  
Mari Hoff ◽  
Matthew A. Brown ◽  
Kristian Hveem ◽  
Oddgeir L. Holmen ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Population Based ◽  
Carrier State ◽  
Nucleotide Polymorphisms ◽  
Hla B27 ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Hunt Study

Objective.The genetic component of ankylosing spondylitis (AS) development is ∼90%. Of the known heritability, ∼20% is explained by HLA-B27, and 113 identified AS-associated single-nucleotide polymorphisms (SNP) account for ∼7.4%. The objectives were to construct a weighted genetic risk score (wGRS) using currently known genome-wide susceptibility SNP, and to evaluate its predictive ability for AS in the Norwegian population-based Nord-Trøndelag Health Study (HUNT).Methods.AS cases (n = 164) and controls (n = 49,032) were from the second (1995–1997) and third (2006–2008) waves of the HUNT study, to which the entire adult population of the northern region of Trøndelag was invited. A wGRS based on 110 SNP weighted by published OR for AS was constructed, representing each person’s carriage of all risk variants. Logistic regression models including the wGRS alone or in combination with HLA-B27 carrier state and other adjustment variables (sex, age, smoking, body mass index, and hypertension) were developed. Discrimination among models was compared using area under the curve (AUC).Results.The wGRS was associated with AS (OR 1.7, 95% CI 1.4–2.1), but showed low discrimination (AUC 0.62, 95% CI 0.58–0.67). HLA-B27 was significantly associated with AS (OR 50, 95% CI 32–81), showing high discrimination (AUC 0.88, 95% CI 0.85–0.90). Combining the wGRS and HLA-B27 improved prediction (AUC 0.90, 95% CI 0.87–0.92; p < 0.001 vs wGRS alone, p < 0.01 vs HLA-B27 alone). Further inclusion of adjustment variables gave a small improvement (AUC 0.91, 95% CI 0.89–0.94; p = 0.03).Conclusion.Prediction in a population-based setting based on all currently known AS susceptibility SNP was better than HLA-B27 carrier state alone, although the improvement was small and of uncertain clinical value.

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