Occupational therapy interventions in promoting social communication skills among children with autism spectrum disorder: A scoping review.

INTRODUCTION: Children with Autism Spectrum Disorder (ASD) often face significant challenges in verbal communication, social interaction, and exhibit repetitive behavioral patterns. These challenges persist across various developmental stages, particularly impacting their social communication abilities. This scoping review aims to explore the range of occupational therapy interventions that are employed to enhance social communication skills in children with ASD. MATERIALS AND METHODS: A literature search was conducted independently on scientific databases: Scopus, Google Scholar, Science Direct, and Web of Science (WOS). The process was carried out according to the PRISMA guidelines. RESULT: Of the 195 studies identified, 8 articles involving 185 participants, aged 17 months to 12 years old, across six countries met the inclusion criteria. The majority of studies indicate significant improvement in social communication abilities, while one study demonstrates insignificant results and another study presents mixed outcomes, utilising two different assessment tools. CONCLUSION: Occupational therapy has showed promise in improving social communication in children with ASD. Nonetheless, this review emphasises the need for greater indepth study and long-term evaluation to better explain and sustain these benefits. More research is needed to develop OT interventions that are both effective and evidence-based.

Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients.

OBJECTIVE: To identify novel biomarker(s) for knee osteoarthritis (OA) using a metabolomics approach. METHOD: We utilized a two-stage case-control study design. Plasma samples were collected from knee OA patients and healthy controls after 8-h fasting and metabolically profiled using a targeted metabolomics assay kit. Linear regression was used to identify novel metabolic markers for OA. Receiver operating characteristic (ROC) analysis was used to examine diagnostic values. Gene expression analysis was performed on human cartilage to explore the potential mechanism for the novel OA marker(s). RESULTS: Sixty-four knee OA patients and 45 controls were included in the discovery stage and 72 knee OA patients and 76 age and sex matched controls were included in the validation stage. We identified and confirmed six metabolites that were significantly associated with knee OA, of which arginine was the most significant metabolite (P < 3.5 × 10(-13)) with knee OA patients having on average 69 µM lower than that in controls. ROC analysis showed that arginine had the greatest diagnostic value with area under the curve (AUC) of 0.984. The optimal cutoff of arginine concentration was 57 µM with 98.3% sensitivity and 89% specificity. The depletion of arginine in OA patients was most likely due to the over activity of arginine to ornithine pathway, leading to imbalance between cartilage repair and degradation. CONCLUSION: Arginine is significantly depleted in refractory knee OA patients. Further studies within a longitudinal setting are required to examine whether arginine can predict early OA changes.

Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis.

OBJECTIVE: To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). METHOD: We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into 'mild' and 'severe' groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. RESULTS: Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10(-5)), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10(-3)). There was no observed association between radiographic severity and HLA-B*27. CONCLUSIONS: These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

The functional MICA-129 polymorphism is associated with skin but not joint manifestations of psoriatic disease independently of HLA-B and HLA-C.

A methionine/valine polymorphism at amino acid 129 of the major histocompatibility complex class I chain-related gene A (MICA-129) categorizes alleles into strong and weak binders of the natural killer (NK) and T-cell receptor NKG2D. We investigated whether MICA-129 is differentially associated with skin and joint manifestations of psoriatic disease (PsD) independently of human leukocyte antigen (HLA)-C and HLA-B in patients and controls from Toronto and St. John's. The MICA-129 methionine (Met) allele, particularly Met/Met homozygosity, was strongly associated with both cutaneous psoriasis (PsC) and psoriatic arthritis (PsA) independently of HLA-B and HLA-C in Toronto patients, and was also associated with PsA in St. John's patients, but with no additional effect of Met/Met homozygosity. No association remained after adjustment for HLA alleles in St. John's patients. MICA-129 was not associated with PsA when compared with PsC. We conclude that MICA-129 is a marker of skin manifestations of PsD that is independent of HLA class I in Toronto patients.

A population-based study of hereditary non-polyposis colorectal cancer: evidence of pathologic and genetic heterogeneity.

Hereditary non-polyposis colorectal cancer (HNPCC) may be the result of Lynch syndrome (LS) caused by mutations in mismatch repair (MMR) genes, a syndrome of unknown etiology called familial colorectal cancer type-X (FCCTX), or familial serrated neoplasia associated with the colorectal cancer (CRC) somatic BRAF mutation. To determine the cause of HNPCC in the founder population of the island of Newfoundland, we studied 37 families with LS and 29 families without LS who fulfilled the Amsterdam I criteria. In non-LS, four index CRCs were BRAF mutation positive, one of which was microsatellite instable. Geographic clustering of LS families caused by three different founder mutations in MSH2 was observed. Nine unique MMR mutations in four MMR genes were identified in single families distributed in different geographic isolates. The geographic distribution of non-LS was similar to LS. The coefficient of relatedness using genotype data was significantly higher for non-LS than for all CRC. Extensive genealogic investigation failed to connect non-LS families and in some clusters pathologic CRC heterogeneity was observed. We conclude that non-LS HNPCC may be a heterogeneous disorder with different pathogenic pathways, and that the geographic distribution is consistent with multiple different mutations in unknown CRC susceptibility gene(s).

Within-season dynamics of red palm mite (Raoiella indica) and phytoseiid predators on two host palm species in south-west India.

Field surveys were conducted monthly between December 2008 and July 2009 in Kerala, south-west India to compare the population dynamics of the red palm mite Raoiella indica (RPM) on two host plants Areca catechu and Cocos nucifera during one non-monsoon season when, in general, RPM populations increase. The aim was to examine the effects of host plant, host plant locality and the impact of climatic factors on RPM and related phytoseiid predators. There were significantly higher RPM densities on areca in peak season (May/June) compared to coconut; although significantly more coconut sites were infested with RPM than areca. Although no one climatic factor was significantly related to RPM numbers, interactions were found between temperature, humidity and rainfall and the partitioning of host plant locality showed that where conditions were warmer and drier, RPM densities were significantly higher. Specifically on coconut, there was a significant relation between RPM densities and the combined interaction between site temperature, site humidity and phytoseiid densities. There was a marked difference in the density of phytoseiids collected between areca and coconut palms, with significantly more on the latter, in several months. Amblyseius largoensis was the most commonly collected phytoseiid in association with RPM, although Amblyseius tamatavensis species group and Amblyseius largoensis species group were collected in association with RPM also. There was also evidence of a weak numerical response of the combined phytoseiid complex in relation to RPM density the previous month on coconut but this was not observed on areca.

Divergent effects of infliximab and anakinra therapies on macrophage phenotype from patients with refractory rheumatoid arthritis.

Previously, we documented the co-expression of the inducible nitric oxide synthase (NOS2) and protein kinase C-eta (PKC-eta) in peripheral blood-derived macrophages (PBDM) from moderate to severe rheumatoid arthritis (RA) patients with elevated plasma nitric oxide levels but not from those with non-inflammatory osteoarthritis (OA) or normal plasma NO levels. The presence of PKC-eta was found to be required before macrophages could acquire the NOS2-positive phenotype and make copious levels of NO. In the current study, we report the divergent effects of two biological-based RA therapies which target TNFalpha function (infliximab) or IL1 response (anakinra) on the development of the NOS2-positive phenotype by PBDM in patients with refractory RA. Both infliximab and anakinra were effective in improving disease symptoms. However, treatment with anakinra, but not infliximab led to a complete suppression of NOS2 expression in PBDM and consequently, a more pronounced reduction in plasma NO levels. Data also revealed a requirement of both TNF-alpha and IL-1 in the development of the NOS2-positive macrophage phenotype. Finally, the data have shed light on the molecular mechanisms by which NO production may be regulated during disease progression to severe RA, and thus, offer a novel insight into the identification of future therapeutic targets for the treatment of inflammatory diseases.

TNF-alpha-308 G/A polymorphism and responsiveness to TNF-alpha blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis.

Although tumor necrosis factor-alpha (TNF-alpha) blockade is a very effective therapy for rheumatoid arthritis (RA), not all patients achieve a favorable outcome. The objective of this study was to determine if the common TNF-alpha variant -308(A) predicts poor response to TNF-alpha inhibitors in RA patients using meta-analysis. Studies were identified using MEDLINE and EMBASE. Data were extracted based on DAS28 or achieving at least American College of Rheumatology 20 response. A total of nine studies met the inclusion criteria representing a total of 692 RA patients. There was no significant heterogeneity among study effect sizes (P=0.36). The frequency of the A allele was 22% (119/531) in responders and 37% (60/161) in non-responders. The odds of having the A allele was lower in responders versus non-responders (odds ratio (OR)=0.43, 95% confidence intervals (CI): 0.28-0.68, P=0.000245), irrespective of the TNF-alpha inhibitor prescribed, indicating that the -308(A) variant predicts poor response to TNF-alpha inhibitors. The clinical utility of prospectively genotyping for this variant when initiating anti-TNF-alpha therapy for RA should now be formally assessed.

Familial aggregation of psoriatic arthritis.

OBJECTIVES: The aim of this study was to determine the recurrence risk of psoriatic arthritis (PsA) and uncomplicated psoriasis in first-degree relatives (FDRs) of patients with PsA. METHODS: All available FDRs (full siblings, parents and children) of 100 consecutive consenting patients attending a PsA clinic were evaluated for the presence of psoriasis and PsA using a standard protocol. The protocol included a screening questionnaire, physical examination by a rheumatologist, and radiographic and laboratory assessment. The prevalence of PsA and psoriasis in FDRs of the index cases was determined, and the recurrence risk ratio (lambda) was calculated, assuming a population prevalence of PsA of 0.25%, and a population prevalence of psoriasis of 2%. RESULTS: The 100 probands had 533 relatives. Eighty-four of them were deceased and 53 were unavailable (age <16 years). Of the remaining 396 FDRs, 107 did not participate (living too far away/did not consent). Thus, 289/396 (73%) of the available FDRs participated in the study. There were 130 siblings, 108 parents and 51 children. The prevalence of PsA and psoriasis among FDRs was 7.6% and 15.2%, respectively. The lambda(1 )was 30.4 for PsA and 7.6 for psoriasis. The prevalence of PsA and psoriasis in siblings was 7.7% and 17.7%, respectively. The lambda(S) was 30.8 for PsA and 8.8 for psoriasis. CONCLUSIONS: The recurrence risk ratio for both PsA and psoriasis is high in FDRs and siblings of patients with PsA. These results confirm that both PsA and psoriasis have a strong heritable component.

Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis.

OBJECTIVES: The aim of the current study was to determine the contribution of interleukin (IL)1 gene cluster polymorphisms previously implicated in susceptibility for ankylosing spondylitis (AS) to AS susceptibility in different populations worldwide. METHODS: Nine polymorphisms in the IL1 gene cluster members IL1A (rs2856836, rs17561 and rs1894399), IL1B (rs16944), IL1F10 (rs3811058) and IL1RN (rs419598, the IL1RA VNTR, rs315952 and rs315951) were genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different centres in 10 countries. Association of variants with AS was tested by Mantel-Haenszel random effects analysis. RESULTS: Strong association was observed with three single nucleotide polymorphisms (SNPs) in the IL1A gene (rs2856836, rs17561, rs1894399, p = 0.0036, 0.000019 and 0.0003, respectively). There was no evidence of significant heterogeneity of effects between centres, and no evidence of non-combinability of findings. The population attributable risk fraction of these variants in Caucasians is estimated at 4-6%. CONCLUSIONS: This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.

Flexible chitosan-nano ZnO antimicrobial pouches as a new material for extending the shelf life of raw meat.

As a breakthrough to open up the industrial use of novel environmentally benign packaging material, we propose the first report on portable chitosan-ZnO nano-composite pouches that will serve as elite entrants in smart packaging. A facile, one pot procedure was adopted for the preparation of the C-ZnC films. In order to tune the property of C-ZnC films, four different composite films were prepared by varying the concentration of ZnO. The prepared films were found to be much superior when compared to bare chitosan and other conventional films. Two bacterial strains that commonly contaminate in packed meat were selected as target microbes to elucidate the antimicrobial activity of the prepared C-ZnO film. Detailed investigations revealed that the antimicrobial efficiency is linearly related to the amount of ZnO nano-particles in the composite. The C-2 films exhibited excellent antimicrobial activity and was fabricated into packaging pouches for raw meat. The prepared pouches showed significant action against the microbes in raw meat owing to its complete inhibition of microbial growth on the sixth day of storage at 4°C. The C-2 pouches stand as a top-notch material when compared to polyethylene bag in extending the shelf life of raw meat.

CTLA-4 Genetic Variants (rs11571317 and rs3087243): Role in Susceptibility and Progression of Breast Cancer.

BACKGROUND: Dysfunctional regulation at immune checkpoints may lead to escape of the tumor cells and gives a scope to set in the unresolved Breast cancer (BC). The major anti-tumor retort is cell-mediated response which involves T lymphocytes. CTLA-4 (Cytotoxic T lymphocyte associated protein-4) with immune suppressive function and tolerance is associated with various autoimmune diseases and cancers including BC. The present study deals with CTLA-4 gene selected polymorphisms (rs11571317 C/T and rs3087243G/A) to explore their relation with breast cancer susceptibility and progression in BC patients. METHODS: For the present case-control study, we recruited a total of 570 women which include breast cancer patients and healthy control women from south India. Blood samples were collected, genomic DNA was isolated and genotyped by using PCR-RFLP method, and the data were analysed through suitable statistics. RESULTS: We observed a significant association of rs11571317 with BC in our study group, where CC genotype showed a three-fold increased risk towards BC and CT genotype to be protective. In-silico analyses strengthened our observation revealing the abolition of SP1 binding site in the CTLA-4 promoter by the mutant allele T. The CTLA-4 rs3087243 polymorphism showed an association not with the susceptibility but towards the tumor progression, where GG genotype was coupled with reduced tumor growth (OR = 0.01) and GA (OR = 6.2), AA (OR = 3.4) with increased tumor growth. The T-G haplotype was found to confer protection against breast cancer risk while C-A (OR = 3.6) and T-A (OR = 15.8) haplotypes were associated with disease progression. In-silico analysis for rs3087243 revealed change in threshold values between reference and variant sequences. CONCLUSION: The study suggests varied roles of different polymorphisms of CTLA-4 in the aetiopathogenesis of BC. Understanding the mechanism may help in the CTLA-4 based immunotherapy for BC.

Medicinal Plants: Their Use in Anticancer Treatment.

Globally cancer is a disease which severely effects the human population. There is a constant demand for new therapies to treat and prevent this life-threatening disease. Scientific and research interest is drawing its attention towards naturally-derived compounds as they are considered to have less toxic side effects compared to current treatments such as chemotherapy. The Plant Kingdom produces naturally occurring secondary metabolites which are being investigated for their anticancer activities leading to the development of new clinical drugs. With the success of these compounds that have been developed into staple drugs for cancer treatment new technologies are emerging to develop the area further. New technologies include nanoparticles for nano-medicines which aim to enhance anticancer activities of plant-derived drugs by controlling the release of the compound and investigating new methods for administration. This review discusses the demand for naturally-derived compounds from medicinal plants and their properties which make them targets for potential anticancer treatments.

Dengue serotype surveillance among patients admitted for dengue in two major hospitals in Selangor, Malaysia, 2010-2011.

Dengue serotype surveillance is important as any changes in serotype distribution may result in an outbreak or increase in severe dengue cases. This study aimed to determine circulating dengue serotypes in two hospitals in Selangor. Serum samples were collected from patients admitted for dengue at these two major public hospitals i.e. Hospital Sungai Buloh (HSB) and Hospital Tunku Ampuan Rahimah (HTAR) between November 2010 and August 2011 and subjected to real-time RT-PCR using SYBR® Green. All four dengue serotypes were detected in samples from both hospitals. The predominating serotype was dengue 1 in samples from both hospitals (HSB, DENV-1; 25.53 % and HTAR, DENV-1; 32.1 %).

Cytotoxic therapy in systemic lupus erythematosus. Experience from a single center.

The present survey of cytotoxic therapy from a single large lupus clinic has shown that approximately 33% of the patients have received cytotoxic therapy at some point in their course. These agents were initiated for a variety of manifestations, with renal manifestations being the major indication, accounting for 28.2% of the cytotoxic agents used. Other common indications for initiation of cytotoxic therapy included steroid sparing (18.4%), global flare (12.5%), neurologic manifestations (11.4%), and musculoskeletal (8.6%). Azathioprine, methotrexate, and cyclophosphamide accounted for 98% of all cytotoxic agents used. Azathioprine was the most frequently used cytotoxic drug (70%), followed by methotrexate (21.5%) and cyclophosphamide (9.4%). Cytotoxic agents were used sequentially in 12.5% of patients and in combination in 4.2% of the patients. Overall, the use of cytotoxic therapy appears to be beneficial in reducing global disease activity, as the mean SLEDAI fell by 2.59 (33%) over 6 months of cytotoxic therapy, and the mean steroid dose was reduced by 37% over the same time period. There was also an improvement in most organ-specific indications with the use of cytotoxic agents. Overall the cytotoxic agents were well tolerated, with 17% of the courses being discontinued due to a side effect. Cytopenia was the most common side effect necessitating discontinuation of cytotoxic agents.

IDDM9 and a locus for rheumatoid arthritis on chromosome 3q appear to be distinct.

Markers near a locus for type 1 diabetes on chromosome 3q22-q25 (IDDM9) demonstrate linkage to rheumatoid arthritis, however it is not clear whether these two loci overlap. Sex-specific linkage analysis may be of interest for rheumatoid arthritis on chromosome 3q since linkage of type 1 diabetes to IDDM9 derives predominantly from affected female sibpairs, and rheumatoid arthritis is more common in females than males. Using data from a recent genome scan for rheumatoid arthritis and sex-specific linkage analysis we show that linkage of rheumatoid arthritis to chromosome 3q peaks approximately 30 cM centromeric to IDDM9. Furthermore, there is no evidence for linkage to IDDM9 in females with rheumatoid arthritis.

HLA-DRB1*04 alleles in psoriatic arthritis: comparison with rheumatoid arthritis and healthy controls.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor. An increased frequency of HLA-DR4 has been noted in PsA, particularly among patients with a rheumatoid arthritis like (RA) arthritis. The aim of the current investigation was to compare HLA-DRB1*04 alleles in patients with PsA, patients with RA, and healthy controls. Sample size calculations based on the frequency of HLA-DR4 suggested that 90 individuals in each patient group would be sufficient to address our question. Therefore, 90 HLA-DRB1*04 positive patients from each patient group underwent high resolution molecular typing and were included in this study. Although HLA-DRB1*0401 was the most frequent allele in all groups, its frequency among the PsA patients was lower than that of RA patients and controls. HLA-DRB1*0402 was higher among patients with PsA. Patients with RA were more likely to have more than one shared epitope allele than either PsA or the healthy control group. HLA-DQB1 alleles did not contribute further information. We suggest that the differences in the class II HLA epitope(s) may also be related to interaction specificity with another molecule functioning in the immune response to a putative arthritogenic antigen and result in differences in disease expression.

Comparison of clinical and immunogenetic features in familial versus sporadic psoriatic arthritis.

OBJECTIVE: To compare patients with familial versus sporadic psoriatic arthritis (PsA) with respect to clinical, radiological and immunogenetic features. METHODS: All patients were identified from the University of Toronto Psoriatic Arthritis Clinic. Familial and sporadic PsA were distinguished based on the proband's self-reported history. The probands were compared at presentation to clinic with respect to: demographic information, age of onset of psoriasis and inflammatory arthritis, disease activity, disease damage, laboratory variables, functional class and HLA antigens. The two groups were compared using a univariate analysis. RESULTS: In total 407 patients were included. Thirty-six patients (8.8%) were eliminated as they reported a family history of arthritis in the absence of psoriasis. Of the remaining 371 patients, 150 patients reported a positive family of either PsA or psoriasis. 221 patients (54.2%) had no family history of psoriatic arthritis, psoriasis, or "arthritis". The familial group were younger at presentation to clinic (p = 0.003), had an earlier age of onset of psoriasis (p = 0.001) and inflammatory arthritis (p = 0.001) and were more likely to be receiving treatment (p = 0.001). The mean number of actively inflamed joints was higher in the sporadic group (p = 0.035), along with a higher frequency of rheumatoid factor positivity (p = 0.04). Only the age of onset variables and medication use retained significance after correction for multiple comparisons. CONCLUSIONS: In comparing probands with familial versus sporadic PsA, we noted a marked difference in the age of onset of psoriasis and inflammatory arthritis, along with other differences in several clinical variables. These differences may be helpful in identifying PsA patients with a stronger genetic predisposition.

Coexistence of Fabry's disease and systemic lupus erythematosus.

This report describes a case of a female with systemic lupus erythematosus, who was subsequently diagnosed with Fabry's disease. Due to similarities in the organs involved by these two multisystem disorders, difficulties were encountered in establishing a prompt diagnosis of Fabry's disease. That and subsequent management of this patient are discussed. A literature review of the coexistence of the two disorders along with the potential pathogenic mechanisms explaining this association are explored.

Association of a specific ERAP1/ARTS1 haplotype with disease susceptibility in ankylosing spondylitis.

OBJECTIVE: Alterations in antigen processing have been proposed to play a significant role in the pathogenesis of ankylosing spondylitis (AS). A non-major histocompatibility complex gene encoding an endoplasmic reticulum aminopeptidase, ERAP1, has been implicated recently. This study assessed 13 coding single-nucleotide polymorphisms (SNPs) from 5 genes involved in antigen processing (ERAP1, TAP1, TAP2, LMP2, and LMP7) in 3 Canadian cohorts of patients with AS, to address the possibility of gene interactions in disease susceptibility. METHODS: The study involved 992 AS cases and 1,437 controls from 3 centers (472 cases and 451 controls from Alberta, 138 cases and 392 controls from Newfoundland, and 382 cases and 594 controls from Toronto). Most of the patients with AS and healthy, unrelated controls were Caucasians of northern European descent. Single-marker and haplotype associations were determined using an allelic likelihood ratio test in UNPHASED, version 3.0.12, and the WHAP program, respectively. P values for significance of haplotype associations were calculated using a permutation test. RESULTS: A specific ERAP1 haplotype, rs27044/10050860/30187-CCT, was strongly associated with increased risk of AS in all 3 case-control cohorts (pooled odds ratio [OR] 1.81, 95% confidence interval [95% CI] 1.46-2.24; P=7x10(-8)), while a second specific ERAP1 haplotype, rs30187/26618/26653-CTG, reduced the disease risk (pooled OR 0.77, 95% CI 0.67-0.88; P=9x10(-5)). Significant associations were also noted for 3 ERAP1 SNP variants (rs10050860, rs30187, and rs26653), although no significant haplotype interaction between ERAP1 and TAP/LMP loci was evident. CONCLUSION: These data indicate that an AS disease locus may reside on a specific ERAP1 haplotype, and its effect is not multiplicative with contributions from TAP and LMP genes.