Association of interleukin-1β genetic polymorphisms with cognitive performance in elderly females without dementia

Interleukin-1β (IL-1β) is considered to have a role in age-related cognitive decline. A recent study has shown that a promoter polymorphism of the IL-1β gene (rs16944) is associated with cognitive performance in elderly males without dementia. In this study, we examined whether polymorphisms of the IL-1β gene also influence cognitive functions in elderly females. Cognitive functions were assessed by the Wechsler adult intelligence scale-revised (WAIS-R) in 99 elderly (60 years) females without dementia. We selected five tagging polymorphisms from the IL-1β gene and examined the associations with the WAIS-R scores. Significant associations were found between verbal intelligence quotient (IQ) and the genotypes of rs1143634 and rs1143633 (P=0.0037 and P=0.010, respectively). No significant associations of rs16944 genotype were found with verbal or performance IQ. However, individuals homozygous for the G allele of rs16944 achieved higher scores in digit span compared with their counterpart, which is consistent with the previous findings in males. These results suggest that IL-1β gene variation may have a role in cognitive functions in aging females as well as males.     

Genetic Structure of Spatial and Verbal Working Memory

Working memory (WM) encompasses both short-term memory (storage) and executive functions that play an essential role in all forms of cognition. In this study, the genetic structure of storage and executive functions engaged in both a spatial and verbal WM span task is investigated using a twin sample. The sample consists of 143 monozygotic (MZ) and 93 dizygotic (DZ) Japanese twin pairs, ages 16 to 29 years. In 155 (87 MZ, 62 DZ) of these pairs, cognitive ability scores from the Kyodai Japanese IQ test are also obtained. The phenotypic relationship between WM and cognitive ability is confirmed (r = 0.26–0.44). Individual differences in WM storage and executive functions are found to be significantly influenced by genes, with heritability estimates all moderately high (43%–49%), and estimates for cognitive ability comparable to previous studies (65%). A large part of the genetic variance in storage and executive functions in both spatial and verbal modalities is due to a common genetic factor that accounts for 11% to 43% of the variance. In the reduced sample, this common genetic factor accounts for 64% and 26% of the variance in spatial and verbal cognitive ability, respectively. Additional genetic variance in WM (7%–30%) is due to modality specific factors (spatial and verbal) and a storage specific factor that may be particularly important for the verbal modality. None of the variance in cognitive ability is accounted for by the modality and storage genetic factors, suggesting these may be specific to WM.     

IL1 receptor accessory protein like,a protein involved in X-linked mental retardation,interacts with Neuronal Calcium Sensor-1 and regulates exocytosis

Previously, human genetics-based approaches allowed us to show that mutations in the IL-1 receptor accessory protein-like gene (IL1RAPL) are responsible for a non-specific form of X-linked mental retardation. This gene encodes a predicted protein of 696 amino acids that belongs to a novel class of the IL-1/Toll receptor family. In addition to the extracellular portion consisting of three Ig-like domains and the intracellular TIR domain characteristic of the IL-1/Toll receptor family, IL1RAPL contains a specific 150 amino acid carboxy terminus that has no significant homology with any protein of known function. In order to begin to elucidate the function of this IL-1/Toll receptor-like protein, we have assessed the effect of recombinant IL1RAPL on the binding affinity of type I IL-1R for its ligands IL-1alpha and beta and searched for proteins interacting with the specific carboxy terminus domain of IL1RAPL. Our results show that IL1RAPL is not a protein receptor for IL-1. In addition we present here the identification of Neuronal Calcium Sensor-1 (NCS-1) as an IL1RAPL interactor. Remarkably, although NCS-1 and its non-mammalian homologue, frequenin, are members of a highly conserved EF-hand Ca(2+) binding protein family, our data show that IL1RAPL interacts only with NCS-1 through its specific C-terminal domain. The functional relevance of IL1RAPL activity was further supported by the inhibitory effect on exocytosis in PC12 cells overexpressing IL1RAPL. Taken together, our data suggest that IL1RAPL may regulate calcium-dependent exocytosis and provide insight into the understanding of physiopathological mechanisms underlying cognitive impairment resulting from IL1RAPL dysfunction.     

The X-linked intellectual disability protein IL1RAPL1 regulates excitatory synapse formation by binding PTPδ and RhoGAP2

Mutations of the Interleukin-1-receptor accessory protein like 1 (IL1RAPL1) gene are associated with cognitive impairment ranging from non-syndromic X-linked mental retardation to autism. IL1RAPL1 belongs to a novel family of IL1/Toll receptors, which is localized at excitatory synapses and interacts with PSD-95. We previously showed that IL1RAPL1 regulates the synaptic localization of PSD-95 by controlling c-Jun N-terminal kinase activity and PSD-95 phosphorylation. Here, we show that the IgG-like extracellular domains of IL1RAPL1 induce excitatory pre-synapse formation by interacting with protein tyrosine phosphatase delta (PTPδ). We also found that IL1RAPL1 TIR domains interact with RhoGAP2, which is localized at the excitatory post-synaptic density. More interestingly, the IL1RAPL1/PTPδ complex recruits RhoGAP2 at excitatory synapses to induce dendritic spine formation. We also found that the IL1RAPL1 paralog, IL1RAPL2, interacts with PTPδ and induces excitatory synapse and dendritic spine formation. The interaction of the IL1RAPL1 family of proteins with PTPδ and RhoGAP2 reveals a pathophysiological mechanism of cognitive impairment associated with a novel type of trans-synaptic signaling that regulates excitatory synapse and dendritic spine formation.     

IL1RAPL1 gene deletion as a cause of X-linked intellectual disability and dysmorphic features

Intellectual disability affects approximately 2% of the population with males outnumbering females due to involvement of over 300 genes on the X chromosome. The most common form of X-linked intellectual disability (XLID) is fragile X syndrome. We report a family with an apparent XLID pattern with the proband, his mother and maternal half brother having an Xp21.3 deletion detected with chromosomal microarray analysis involving the interleukin 1 receptor accessory protein-like 1 (IL1RAPL1) gene. IL1RAPL1 is highly expressed in the postnatal brain, specifically hippocampus suggesting a specialized role in memory and learning abilities. The proband presented with intellectual disability, a broad face, prominent and wide nasal root, ptosis, a wide philtrum and a small mouth. XLID due to involvement of the IL1RAPL1 gene has been reported to cause nonsyndromic XLID. We report a new family with XLID due to partial deletion of IL1RAPL1, summarize reported literature and describe similar phenotypic similarities among the affected individuals in this family and those reported in the literature proposing that deletion of IL1RAPL1 may cause syndromic XLID. Additional reports are needed to further characterize whether syndromic features are related to disturbances of this gene.     

Age at natural menopause and cognition

OBJECTIVES: To examine associations between age at natural menopause, childhood IQ and cognition at age 65 years. To determine if lower age at menopause partly mediates the effect of childhood IQ on cognition at age 65 years. METHODS: Data were provided by a sub-cohort of women participating in a longitudinal study of brain ageing and health. Main variables were childhood IQ from a 1947 national survey of children born in 1936, age at natural menopause and five cognitive tests measured in 2000-2001. RESULTS: Age at menopause was associated with childhood IQ (r = 0.221, P = 0.008) and with general cognitive function age 65 years (r = 0.246, P = 0.004). Multiple regression showed 44.4% of the reliable variance in cognitive ability age 65 years is contributed by IQ at an age of 11 years to which, years of education contributed an additional 3.9%. Structural equation modelling suggested that childhood IQ differences contribute 4.8% of the variance to age at natural menopause and that the relation between age at menopause and cognition at age 65 years was accounted for by childhood IQ. CONCLUSION: Childhood IQ and age at menopause each have significant relations with general cognitive function age 65 years but the link between cognition age 65 years and age at menopause might be wholly explained by childhood IQ. The association between childhood IQ and age at menopause may be attributed to central neural mechanisms or, as argued here, to the effects of childhood IQ on adult general health.     

Deletion of the immunoglobulin domain of IL1RAPL1 results in nonsyndromic X-linked intellectual disability associated with behavioral problems and mild dysmorphism

X-Linked intellectual disability accounts for a significant fraction of males with cognitive impairment. Many of these males present with a non-syndromic phenotype and presently mutations in 17 X-linked genes are associated with these patients. Mutations in IL1RAPL1 have been found in multiple families with non-syndromic X-linked intellectual disability. All of the published mutations predict loss of function of the protein. We have identified an additional two families with deletions of a portion of the gene that give rise to cognitive impairment, as well as some behavioral problems and mild dysmorphism. Our clinical findings better delineate the phenotypic spectrum associated with IL1RAPL1 mutations.     

Genetic sources of covariation among P3(00) and online performance variables in a delayed-response working memory task

Genetic and environmental sources of covariation among the P3(00) and online performance elicited in a delayed-response working memory task, and psychometric IQ assessed by the multidimensional aptitude battery, were examined in an adolescent twin sample. An association between frontal P3 latency and task performance (phenotypic r=-0.33; genotypic r=-0.49) was indicated, with genes (i.e. twin status) accounting for a large part of the covariation (>70%). In contrast, genes influencing P3 amplitude mediated only a small part (2%) of the total genetic variation in task performance. While task performance mediated 15% of the total genetic variation in IQ (phenotypic r=0.22; genotypic r=0.39) there was no association between P3 latency and IQ or P3 amplitude with IQ. The findings provide some insight into the inter-relationships among psychophysiological, performance and psychometric measures of cognitive ability, and provide support for a levels-of-processing genetic model of cognition where genes act on specific sub-components of cognitive processes.     

芪参复康胶囊对重度抑郁症患者智力及事件相关电位的影响

目的 探讨中药芪参复康胶囊治疗重度抑郁症患者前后的临床症状、智力、P3潜伏期和波幅的变化.方法 将45例重度抑郁症患者随机分为芪参复康胶囊治疗组(试验组22例)及氟西汀治疗组(氟西汀组23例),对两组在治疗前和治疗后8周评定17项汉密尔顿抑郁量表(HAMD)、韦氏成人智力及进行P300检查,并与22名健康志愿者(对照组)进行比较.结果 ①治疗后试验组和氟西汀组HAMD得分均显著下降(t=6.03,5.12;P＜0.05);②与治疗前相比,试验组和氟西汀组治疗后言语智商、操作智商和总智商的成绩均显著升高(t=4.01,5.36,4.79,3.52,3.90,4.04;P＜0.05).治疗前与对照组相比,试验组和氟西汀组言语智商、操作智商和总智商的成绩均显著降低(t=4.25,4.83,4.42,4.22,4.91,4.30;P＜0.05);治疗后试验组和氟西汀组操作智商均仍低于对照组(t=2.02,2.51,P＜0.05),言语智商和总智商分与对照组相当;治疗后试验组操作智商显著高于氟西汀组(t=2.10,P＜0.05),言语智商差异不显著;③与治疗前相比,试验组和氟西汀组治疗后P3潜伏期均显著缩短(F=4.66,4.20;P＜0.05)、波幅均显著升高(F=5.88,5.47;P＜0.05).治疗前与对照组相比,试验组、氟西汀组P3潜伏期均延迟(F=3.90,3.89;P＜0.05),波幅均降低(F=4.13,4.10;P＜0.05);治疗后,试验组P3潜伏期、波幅均差异不显著;氟西汀组P3潜伏期差异不显著,P3波幅仍偏低(F=2.03,P＜0.05).结论 芪参复康胶囊治疗抑郁症患者后临床症状明显缓解、认知功能有明显改善,其中智力改善疗效肯定,芪参复康胶囊改善操作智商优于氟西汀.     

TM4SF2 gene involvement reconsidered in an XLMR family after neuropsychological assessment

The TM4SF2 gene (localized at Xp11.4 between the loci DXS564 and DXS556) has been found to be mutated in one MRX family. In order to define the corresponding behavioral phenotype, global IQ and specific cognitive skills were assessed in seven males and three females of this family, independent of subject status. Mental retardation (MR) was mild in three patients and moderate in three others. Despite the broad variability of severity of MR, a cognitive profile specific to the MR in this family was documented. It was characterized by language disorder that was more marked in the articulatory component and spatial/verbal short-term memory dissociation with larger mnemonic span for spatial than for verbal cues. Linkage analysis was then performed on the basis of the cognitively determined status. Recombinations were observed with the loci DXS556 at Xp11.4 and DXS441 at Xq13.2 (maximum LOD score = 2.23 at theta = 0 for ALAS2). This localization region does not include the TM4SF2 gene that has been found mutated in both patients with MR and in one non-MR male subject of this family. The present results suggest two main hypotheses. First, TM4SF2 gene mutation could be involved in MR in this family, therefore representing accentuated intra familial phenotypic variability. Second, the structural particularity detected in the TM4SF2 gene might reflect a rare polymorphism rather than a pathogenic mutation, with the gene responsible for MR in this family being therefore more likely to be searched for in the pericentromeric region of the X chromosome.     

Intragenic deletions of IL1RAPL1: Report of two cases and review of the literature

IL1RAPL1 (interleukin-1 receptor accessory protein-like 1) located at Xp21.3-22.1 has repeatedly been shown to be deleted in patients with a contiguous gene syndrome also affecting neighboring genes, in particular DMD (dystrophin), DAX-1 (NR0B1, nuclear receptor subfamily 0, group B, member 1), and GK (glycerol kinase). In contrast, intragenic deletions of IL1RAPL1 or other mutations or cytogenetic aberrations affecting IL1RAPL1 have only rarely been identified. Up to date, they have mostly been associated with nonspecific mental retardation (MRX). We report on two nonrelated patients with MR and additional dysmorphic features who both show intragenic deletions of IL1RAPL1, one of them being de novo (exon 2) and the other one being inherited from his mother (exons 3-5). Deletions were identified by microarray-based chromosome analysis and confirmed by multiplex PCR and FISH, respectively. These data, along with recent functional studies indicating its role in neuronal development, provide further evidence for the relevance of IL1RAPL1 in the pathogenesis of X-linked MR and add knowledge to the phenotypic spectrum of IL1RAPL1 mutations.     

Patterns of memory dysfunction among children surviving temporal lobe tumors.

We compared the cognitive functioning of seven children with left and seven children with right temporal lobe tumors one year or more following completion of medical intervention (surgical resection + radiation therapy). No differences were found between the two groups with respect to verbal IQ, performance IQ.full scale IQ, verbal minus performance IQ, or verbal comprehension, perceptual organization, or freedom from distractability factor scores. After adjusting memory test results for variance attributable to general intelligence, three children with left and four children with right temporal tumors exhibited specific auditory-verbal memory dysfunction; five of these children had concurrent visual-verbal memory dysfunction. Children receiving radiation therapy to the tumor were at significantly greater risk for verbal memory problems. Reading and spelling achievement were significantly correlated with verbal memory performance. Inconsistent association between cerebral hemisphere of tumor and type of cognitive deficit may be related to the relatively slow progression of the tumor and regional interventions such as radiation therapy. Nevertheless, the results of the present report suggest that the majority of children diagnosed with temporal lobe tumors are at increased risk for memory dysfunction and academic failure.     

Mutations in the calcium-related gene IL1RAPL1 are associated with autism

In a systematic sequencing screen of synaptic genes on the X chromosome, we have identified an autistic female without mental retardation (MR) who carries a de novo frameshift Ile367SerfsX6 mutation in Interleukin-1 Receptor Accessory Protein-Like 1 (IL1RAPL1), a gene implicated in calcium-regulated vesicle release and dendrite differentiation. We showed that the function of the resulting truncated IL1RAPL1 protein is severely altered in hippocampal neurons, by measuring its effect on neurite outgrowth activity. We also sequenced the coding region of the close related member IL1RAPL2 and of NCS-1/FREQ, which physically interacts with IL1RAPL1, in a cohort of subjects with autism. The screening failed to identify non-synonymous variant in IL1RAPL2, whereas a rare missense (R102Q) in NCS-1/FREQ was identified in one autistic patient. Furthermore, we identified by comparative genomic hybridization a large intragenic deletion of exons 3-7 of IL1RAPL1 in three brothers with autism and/or MR. This deletion causes a frameshift and the introduction of a premature stop codon, Ala28GlufsX15, at the very beginning of the protein. All together, our results indicate that mutations in IL1RAPL1 cause a spectrum of neurological impairments ranging from MR to high functioning autism.     

A Genetic Investigation of the Covariation Among Inspection Time, Choice Reaction Time, and IQ Subtest Scores

Information processing speed, as measured by elementary cognitive tasks, is correlated with higher order cognitive ability so that increased speed relates to improved cognitive performance. The question of whether the genetic variation in Inspection Time (IT) and Choice Reaction Time (CRT) is associated with IQ through a unitary factor was addressed in this multivariate genetic study of IT, CRT, and IQ subtest scores. The sample included 184 MZ and 206 DZ twin pairs with a mean age of 16.2 years (range 15-18 years). They were administered a visual (pi-figure) IT task, a two-choice RT task, five computerized subtests of the Multidimensional Aptitude Battery, and the digit symbol substitution subtest from the WAIS-R. The data supported a factor model comprising a general, three group (verbal ability, visuospatial ability, broad speediness), and specific genetic factor structure, a shared environmental factor influencing all tests but IT, plus unique environmental factors that were largely specific to individual measures. The general genetic factor displayed factor loadings ranging between 0.35 and 0.66 for the IQ subtests, with IT and CRT loadings of -0.47 and -0.24, respectively. Results indicate that a unitary factor is insufficient to describe the entire relationship between cognitive speed measures and all IQ subtests, with independent genetic effects explaining further covariation between processing speed (especially CRT) and Digit Symbol.     

X染色体四个STR基因座的遗传多态性及法医学意义

目的 建立X染色体短串联重复序列DXS7133、GATA198A10、DXS9896、DXS6797基因座的复合扩增系统，调查成都汉族人群的遗传多态性并探讨其法医学应用价值。方法 应用PCR和非变性聚丙烯酰胺凝胶电泳分型技术，并检验各基因座女性基因型频率分布是否符合hardy-Weinberg平衡，计算法医学常用各种概率。结果 DXS7133、GATA198A10、DXS9896、DXS6797基因座在成都地区汉族群体中(男100，女120)分别发现6、6、11、8个等位基因，女性个人识别几率分别达0．7962、0．8021、0．9675和0．9444。X^2检验表明各基因座女性的基因型频率分布符合Hardy-Weinherg平衡。32个亲子鉴定案例调查表明这4个基因座符合X染色体伴性遗传方式，未发现突变。结论 DXS7133、GATA198A10、DXS9896、DXS6797基因座在成都汉族群体中具有较高的遗传多态性，适用于个人识别和女孩的亲权鉴定。     

IL1RAPL1 is associated with mental retardation in patients with complex glycerol kinase deficiency who have deletions extending telomeric of DAX1

IL1RAPL1 (interleukin-1 receptor accessory protein-like, gene 1) has recently been shown to be mutated in patients with X-linked mental retardation. Clinical experience has suggested that patients with the contiguous gene syndrome, complex glycerol kinase deficiency (cGKD), will have mental retardation (MR) if they have deletions extending from the GK gene into the DMD gene and/or involving a significant extension telomeric from DAX1. We examined cell lines from patients with cGKD whose clinical features would be informative and would allow us to determine if IL1RAPL1 deletions can help to explain the MR in patients with deletions extending telomeric from DAX1. Our results showed that nearly all patients with deletions involving DAX1, but not DMD, had MR if IL1RAPL1 was deleted. If ILIRAPLI and DMD were intact, the patients with DAX1 deletions only rarely had normal development. Deletions in DNA from patients with cGKD who exhibited MR and had normal IL1RAPL1 all involved the GK and DMD genes. Our data are consistent with the association of IL1RAPL1 gene deletion and MR in the majority of patients with cGKD and deletions extending telomeric from DAX1.     

IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn's disease and correlation with sub-phenotypes

Recent genomic research has identified interleukin-23 receptor (IL23R), nucleotide-binding oligomerization domain containing 2 caspase-activation recruitment domain?15 (NOD2/CARD15), autophagy related 16-like 1 (ATG16L1) and paired-like homeobox 2b (PHOX2B) as susceptibility loci for Crohn's Disease (CD). Our aim was to investigate these gene variants in a group of CD patients and to analyse the correlation to sub-phenotypes such as gender, smoking habits, disease behaviour at diagnosis, severity of disease and extra-intestinal manifestations. Nineteen patients with CD and 20 healthy controls were included in the study. The gene variants IL23R rs7517847 and rs11209026, NOD2/CARD15 rs2066845, PHOX2B rs16853571, ATG16L1 rs2241879 and rs2241880 were genotyped by PCR followed by sequencing. The frequency of the G risk allele of IL23R rs7517847 was found to be increased in patients with CD (42%) compared to that in control subjects (20%) [odds ratio (OR), 2.9; 95% confidence interval [CI], 1.06-7.9; P=0.03]. In addition, the homozygous condition GG was also associated with CD (OR, 8.70; 95% CI, 0.9-81.6; P=0.038). The analysis of correlation of genotype to sub-phenotypes showed an association of ATG16L1 rs2241879 with the lack of extra-intestinal manifestations (OR, 0.03; 95% CI, 0.002-0.45; P=0.006), and the patients defined as non-smokers displayed an increased frequency of the risk allele C (P=0.03). The present study confirms the association of the heterozygous and homozygous IL23R rs7517847 variant with CD and suggests an additive effect of smoking to the ATG16L1 rs2241879 C risk allele SNP, in the context of the multifactorial model established for the development of CD and a protective effect of the same allele against extra-intestinal manifestations.     

Two novel members of the interleukin-1 receptor gene family, one deleted in Xp22.1-Xp21.3 mental retardation

X-linked mental retardation is estimated to affect approximately 1 in 600 males. Although numerous genes responsible for syndromic mental retardation have been identified, the study of non-syndromic mental retardation suffers from intrinsic issues of genetic heterogeneity. During the investigation of three brothers with a contiguous gene deletion syndrome of Becker muscular dystrophy, glycerol kinase deficiency, congenital adrenal hypoplasia, and mental retardation, we found their dystrophin gene to be fused tail-to-tail with a gene encoding a novel member of the interleukin-1 receptor family, IL1RAPL1. This gene has a close relative in Xq22, which we call IL1RAPL2. Both IL1RAPL1 and IL1RAPL2 have novel C-terminal sequences not present in other related proteins, and are encoded by very large genes. The 1.8-megabase deletion in these patients removes not only the last exon of the dystrophin gene, the entire glycerol kinase and DAX-1 genes, and the MAGE-B gene cluster, but also three exons encoding the intracellular signalling domain of IL1RAPL1. The literature contains multiple reports of patients with non-syndromic mental retardation in association with an Xp22.1-Xp21.3 microdeletion of a marker which lies within the IL1RAPL1 gene. The gene is also wholly or partially deleted in patients with mental retardation as part of a contiguous deletion syndrome. We suggest that IL1RAPL1, and perhaps IL1RAPL2, are strong candidates for X-linked non-syndromic mental retardation loci, and that molecules resembling IL-1 and IL-18 play a role in the development or function of the central nervous system.     

Genetic Covariance Structure of Reading,Intelligence and Memory in Children

This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained by a common genetic factor for reading performance, IQ, WM and STM and a genetic factor that only influenced reading performance and verbal memory. Genetic variation explained 83% of the variation in reading performance; most of this genetic variance was explained by variation in IQ and memory performance. We hypothesize, based on these results, that children with reading problems possibly can be divided into three groups: (1) children low in IQ and with reading problems; (2) children with average IQ but a STM deficit and with reading problems; (3) children with low IQ and STM deficits; this group may experience more reading problems than the other two. Edited by Chandra Reynolds.     

白介素受体相关激酶-1基因多态性与类风湿关节炎的相关性

目的探讨白介素受体相关激酶-1(IRAK1)rs3027898和rs1059703多态性性与类风湿关节炎(RA)易感性及临床参数的关系。方法收集RA患者123例和体检的220名健康对照者外周血标本,采用聚合酶链反应-连接酶检测反应(PCR-LDR)方法检测IRAK1 rs3027898和rs1059703基因多态性,收集并计算RA患者临床参数:发病年龄、性别、RF抗体、抗CCP抗体、RA疾病活动(DAS28≥3.2)、骨破坏和用药情况。结果 RA组IRAK1 rs3027898和rs1059703的基因型频率和等位基因频率与健康对照组比较,差异无统计学意义(P>0.05)。RA患者IRAK1 rs3027898和rs1059703基因型与发病年龄、性别、RF抗体和抗CCP抗体阳性率、骨破坏阳性率均无相关性(P>0.05)。RA患者IRAK1 rs3027898基因型与RA疾病活动无相关性(P>0.05),RA患者IRAK1 rs1059703基因型与RA疾病活动存在相关性(P<0.05),携带CT+TT基因型RA患者疾病活动的风险是携带CC基因型RA患者4.243倍(P=0.023,OR=4.243,95%CI为1.223～14.715)。结论我国汉族人群中,IRAK1 rs3027898和rs1059703多态性与RA的易感性无关,但IRAK1 rs1059703多态性可能是RA患者疾病活动的一个遗传危险因素。