Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis?
Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis?
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DOI：
10.1002/acr.21601
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发表时间：
2012-05
影响因子：
4.7
通讯作者：
Assassi, Shervin
中科院分区：
文献类型：
--
作者：
Joshi, Reeti;Reveille, John D.;Brown, Matthew A.;Weisman, Michael H.;Ward, Michael M.;Gensler, Lianne S.;Wordsworth, B. Paul;Evans, David M.;Assassi, Shervin
强直性脊柱炎(AS)的几个遗传风险变异已经在全基因组关联研究中被确定。我们的目标是检查家族性AS病例是否具有较高的这些易感变异的遗传负荷。总体而言，502名AS患者接受了检查，其中312人有AS的一级亲属(FDR)(家族性)，190人没有FDR伴AS或脊柱性关节炎(散发性)。所有患者和受影响的FDR都符合修改后的纽约AS标准。这些患者是从两个美国队列(NASC和Psoas)以及英国-牛津队列招募的。比较家族性和散发性病例中IL23R、IL1R2、ANTRX2、ERAP1、2p15和21q22两个基因间隔区AS易感基因的频率，以及标记SNP rs4349859确定的人类白细胞抗原B27状态。SNPs与多胎状态的关联通过Logistic回归控制兄弟姐妹的大小来评估。HLA-B27在家族性AS中的分布显著高于散发性AS(P=0.0001，OR：4.44，CI：(2.06~9.55))。此外，染色体21q22间隔区的AS危险等位基因在复发性病例中有增加的趋势(p=0.08)。在家族性和散发性病例中，其他风险变异的频率没有显著差异，无论是单独的还是合并的。HLA-B27在家族性AS患者中的分布高于散发性AS患者，提示在HLA-B27阳性的AS患者中，AS的家族聚集性较高。最近报道的非MHC易感基因座在散发性和家族性AS患者中的频率没有明显差异。
Several genetic risk variants for ankylosing spondylitis (AS) have been identified in genome wide association studies. Our objective was to examine whether familial AS cases have a higher genetic load of these susceptibility variants. Overall, 502 AS patients were examined, consisting of 312 who had first-degree relatives (FDR) with AS (familial) and 190 who had no FDR with AS or spondyloarthritis (sporadic). All patients and affected FDRs fulfilled the modified New York Criteria for AS. The patients were recruited from two U.S. cohorts (NASC and PSOAS) and from the United Kingdom- Oxford cohort. The frequencies of AS susceptibility loci in IL23R, IL1R2, ANTRX2, ERAP1, two intergenic regions on chromosomes 2p15 and 21q22, and HLA-B27 status as determined by the tag SNP rs4349859 were compared between familial and sporadic cases. Association between SNPs and multiplex status was assessed by logistic regression controlling for sibship size. HLA-B27 was significantly more prevalent in familial than sporadic cases of AS (p=0.0001, OR: 4.44, CI: (2.06–9.55)). Furthermore, the AS risk allele at chromosome 21q22 intergenic region showed a trend towards higher frequency in the multiplex cases (p=0.08). The frequency of the other AS risk variants did not differ significantly between familial and sporadic cases, either individually or combined. HLA-B27 is more prevalent in familial than sporadic cases of AS, demonstrating higher familial aggregation of AS in patients with HLA-B27 positivity. The frequency of the recently described non-MHC susceptibility loci is not markedly different between the sporadic and familial cases of AS.
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影响因子：
--
作者：
CALIN, A;KENNEDY, LG;WILL, R
通讯作者：
WILL, R
影响因子：
2.1
作者：
Li, Yun;Willer, Cristen J.;Ding, Jun;Scheet, Paul;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
影响因子：
--
作者：
Brown, MA;Kennedy, LG;Wordsworth, P
通讯作者：
Wordsworth, P
影响因子：
3.9
作者：
Brionez, Tamar F.;Assassi, Shervin;Nicassio, Perry
通讯作者：
Nicassio, Perry
影响因子：
--
作者：
Zhang, G;Luo, JC;Reveille, JD
通讯作者：
Reveille, JD