Grant Struan Fa, Petri Michelle, Bradfield Jonathan P, Kim Cecilia E, Santa Erin, Annaiah Kiran, Frackelton Edward C, Glessner Joseph T, Otieno F George, Shaner Julie L, Smith Ryan M, Eckert Andrew W, Chiavacci Rosetta M, Imielinski Marcin, Sullivan Kathleen E, Hakonarson Hakon
Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA ; Department of Pediatrics and Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA ; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Appl Clin Genet. 2009 Dec 9;2:1-5. doi: 10.2147/tacg.s4089. Print 2009.
Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs10516487, within the B-cell gene BANK1 and systemic lupus erythematosus (SLE) as a consequence of a genome wide association study of this disease in European and Argentinean populations. In a bid for replication, we examined the effects of the R61H non-synonymous variant with respect to SLE in our genotyped American cohorts of European and African ancestry. Utilizing data from our ongoing genome-wide association study in our cohort of 178 Caucasian SLE cases and 1808 Caucasian population-based controls plus 148 African American (AA) SLE cases and 1894 AA population-based controls we investigated the association of the previously described non-synonymous SNP at the BANK1 locus with the disease in the two ethnicities separately. Using a Fisher's exact test, the minor allele frequency (MAF) of rs10516487 in the Caucasian cases was 22.6% while it was 31.2% in Caucasian controls, yielding a protective odds ratio (OR) of 0.64 (95% CI 0.49-0.85; one-sided p = 7.07 × 10(-4)). Furthermore, the MAF of rs10516487 in the AA cases was 18.7% while it was 23.3% in AA controls, yielding a protective OR of 0.75 (95% CI 0.55-1.034; one-sided p = 0.039). The OR of the BANK1 variant in our study cohorts is highly comparable with that reported previously in a South American/European SLE case-control cohort (OR = 0.72). As such, R61H in the BANK1 gene confers a similar magnitude of SLE protection, not only in European Americans, but also in African Americans.
最近，在针对欧洲和阿根廷人群的系统性红斑狼疮（SLE）全基因组关联研究中，发现B细胞基因BANK1内的单核苷酸多态性（SNP）rs10516487与系统性红斑狼疮之间存在关联。为了进行验证，我们在我们基因分型的欧洲和非洲裔美国人群队列中研究了R61H非同义变体对SLE的影响。利用我们正在进行的全基因组关联研究数据，该研究涉及178例白种人SLE病例和1808例以白种人为基础的对照人群，以及148例非裔美国人（AA）SLE病例和1894例以非裔美国人为基础的对照人群，我们分别研究了BANK1基因座上先前描述的非同义SNP与这两个种族疾病的关联。使用Fisher精确检验，rs10516487在白种人病例中的次要等位基因频率（MAF）为22.6%，而在白种人对照中为31.2%，产生的保护比值比（OR）为0.64（95%CI 0.49 - 0.85；单侧p = 7.07×10⁻⁴）。此外，rs10516487在AA病例中的MAF为18.7%，而在AA对照中为23.3%，产生的保护OR为0.75（95%CI 0.55 - 1.034；单侧p = 0.039）。我们研究队列中BANK1变体的OR与先前在南美/欧洲SLE病例对照队列中报告的OR高度可比（OR = 0.72）。因此，BANK1基因中的R61H不仅在欧裔美国人中，而且在非裔美国人中都赋予了相似程度的SLE保护作用。
