Nath Swapan K, Namjou Bahram, Kilpatrick Jeff, Garriott C Philip, Bruner Gail R, Scofield R Hal, Harley John B
Genetic Epidemiology Unit, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
J Investig Dermatol Symp Proc. 2004 Jan;9(1):64-7. doi: 10.1111/j.1087-0024.2004.00830.x.
Systemic Lupus Erythematosus (SLE), a chronic, complex disease, is the prototype for systemic human autoimmune diseases. Although environmental factors are crucial in triggering the condition, twin and family studies, as well as genetic linkage and association studies, have established its strong genetic predisposition. During the past few years, there has been considerable interest in identifying genomic segments linked to SLE through either a whole genome scan or a candidate gene approach. The discoid lupus erythematosus (DLE) skin lesion is one of the major, and discriminating, manifestations in SLE, especially in African American patients. In this study we have identified 58 multiplex families--27 African American, 26 European American, and 5 others--where at least one SLE patient is also reported to be afflicted with DLE. These families were chosen from the collection of families that are part of our ongoing linkage study for SLE. A genome-wide parametric and nonparametric linkage analysis was conducted with 320 markers. Significant evidence of linkage was identified in only one chromosomal location, 11p13, in the African American families. The maximum 2-point linkage was 5.6 in these pedigrees, obtained at a marker located 47 CM away from the pterminal end of chromosome 11. The peak multipoint LOD score of 4.6 was obtained very nearby. The segregation of this gene suggests dominant inheritance. These results reveal an important genetic effect related to discoid rash at 11p13 in African Americans with SLE, and demonstrate, through increasing genetic homogeneity, the power of pedigree stratification to detect linkage in complex diseases.
系统性红斑狼疮（SLE）是一种慢性、复杂的疾病，是人类系统性自身免疫性疾病的原型。尽管环境因素在引发该病中至关重要，但双胞胎和家族研究以及基因连锁和关联研究已证实其有很强的遗传易感性。在过去几年中，人们对通过全基因组扫描或候选基因方法来确定与SLE相关的基因组片段产生了浓厚兴趣。盘状红斑狼疮（DLE）皮肤病变是SLE的主要且具有鉴别意义的表现之一，在非裔美国患者中尤为如此。在本研究中，我们确定了58个多重家庭——27个非裔美国人家庭、26个欧裔美国人家庭和5个其他家庭——其中至少有一名SLE患者也被报告患有DLE。这些家庭是从我们正在进行的SLE连锁研究的家庭集合中挑选出来的。使用320个标记进行了全基因组参数和非参数连锁分析。在非裔美国人家庭中，仅在一个染色体位置11p13发现了显著的连锁证据。在这些家系中，最大两点连锁值为5.6，在距离11号染色体p末端47厘摩处的一个标记上获得。在附近获得了4.6的最高多点LOD分数。该基因的分离表明为显性遗传。这些结果揭示了与患有SLE的非裔美国人11p13处盘状皮疹相关联的重要遗传效应，并通过增加遗传同质性证明了家系分层在检测复杂疾病连锁中的作用。
