Anaya Juan-Manuel, Rivera Dora, Palacio Luis G, Arcos-Burgos Mauricio, Correa Paula A
Cellular Biology and Immunogenetic Unit, Corporación para Investigaciones Biológicas (CIB), Cra. 72-A No. 78 B-141, Medellin, Colombia.
J Rheumatol. 2003 Oct;30(10):2152-6.
To examine genetic variations in the region surrounding loci of the major histocompatibility complex, and to investigate the probable location of a new candidate region on the short arm of chromosome 6 predisposing to primary Sjögren's syndrome (SS).
We conducted an association study and positional candidate gene approach by microsatellite analysis. Five polymorphic microsatellite markers, D6S273, D6S439, D6S1645, D6S291, and DS61019, spanning the region 6p21.3, and establishing particular landmarks to discriminate between the human leukocyte antigen class II and tumor necrosis factor-a loci, were genotyped by polymerase chain reaction technique.
A total of 64 patients with primary SS and 120 matched controls were examined. There was no genetic stratification among cases and controls. Genotype distribution analysis disclosed a significantly higher number of homozygotes for D6S439 locus in patients than in controls [odds ratio (OR): 3, 95% confidence interval (CI): 1.46-6.14, p = 0.004]. Confirmation of this homozygosity was established by the gene correlation intra-locus test (Fis value = +0.233, p = 0.0007). Allele D6S439*274 was associated to disease (OR: 3, 95% CI: 1.35-6.65, p = 0.006, pc = 0.04). Among patients, no significant linkage disequilibrium (LD) value was found between the studied microsatellites and TAP, HLA-DRB1, or HLA-DQB1 loci. In controls, there was LD between D6S1645 and D6S291 loci.
Our results indicate that D6S439 microsatellite defines a new susceptibility region for primary SS, independent of LD with TAP and HLA DQ/DR. These findings might imply that a gene surrounding this location is causally related to the disease.
研究主要组织相容性复合体基因座周围区域的遗传变异，并探究6号染色体短臂上一个新的原发性干燥综合征（SS）易感候选区域的可能位置。
我们通过微卫星分析进行了一项关联研究和定位候选基因方法。采用聚合酶链反应技术对跨越6p21.3区域、用于区分人类白细胞抗原II类和肿瘤坏死因子-α基因座的5个多态性微卫星标记D6S273、D6S439、D6S1645、D6S291和DS61019进行基因分型。
共检查了64例原发性SS患者和120例匹配对照。病例组和对照组之间没有遗传分层。基因型分布分析显示，患者中D6S439基因座的纯合子数量显著高于对照组[优势比（OR）：3，95%置信区间（CI）：1.46 - 6.14，p = 0.004]。通过基因相关性基因座内检验证实了这种纯合性（Fis值 = +0.233，p = 0.0007）。等位基因D6S439*274与疾病相关（OR：3，95% CI：1.35 - 6.65，p = 0.006，pc = 0.04）。在患者中，所研究的微卫星与TAP、HLA - DRB1或HLA - DQB1基因座之间未发现显著的连锁不平衡（LD）值。在对照组中，D6S1645和D6S291基因座之间存在LD。
我们的结果表明，D6S439微卫星定义了一个新的原发性SS易感区域，与TAP和HLA DQ/DR的LD无关。这些发现可能意味着该位置周围的一个基因与疾病存在因果关系。
