OUTCOME OF SLE IN MINORITIES--NATURE VS NURTURE

越来越多的数据表明，遗传因素，特别是基因， 主要组织相容性复合体，影响病程， 风湿性疾病的预后。 同样，最近的工作证明， 社会经济因素在这些疾病的结果中的重要性。 系统性红斑狼疮（SLE）是一种变异性很大的疾病 其患病率、发病率和死亡率均高于 在少数群体中。 本建议旨在探讨 通过检查SLE少数群体的潜在高发病率， 社会经济、人口、文化、免疫遗传和 临床变量对早期结果的影响 西班牙裔、非裔美国人和白人SLE患者，来自2 地理区域（德克萨斯州休斯顿和阿拉巴马州伯明翰）。 由于大多数遗传 SLE的研究主要集中在欧洲血统的高加索人， 受到连锁不平衡的限制， 同质种族群体 因此，HLA II类基因型（HLA-DRB 1， DRB 3、DRB 5、DQA 1、DQB 1和DPB 1等位基因）将通过 寡分型及其基因剂量，以及III类C4和C2 蛋白质同种异型将在80名西班牙裔，80名非洲裔， 美国人和80名白人连续入组研究。 的 不同种族和民族的SLE检查不仅 使我们有机会更好地确定特定基因的作用， 在SLE的发病机制，但允许独特的机会，检查 其他与种族有关的因素-如卫生保健 行为、依从性、教育和合并症-以确定 遗传和社会文化因素在SLE预后中的相互作用 少数民族和非少数民族。 5年或以下患者 疾病持续时间将从现有的狼疮登记处招募， 位于伯明翰的亚拉巴马大学和德克萨斯大学 休斯顿健康科学中心（UTHSC），该中心正在扩建， 确保完整的案件查明。 西班牙裔患者将被招募 在UTHSC（和UT医疗分支在加尔维斯顿），而非洲裔美国人 将在UAB和UTHSC招募白人患者。 结果 这些措施将在三年内每半年进行一次评估。 结果， 被检查是敏感的早期变化，包括频率和 发作的严重程度、疾病活动性（SLAM）和严重程度（SLICC），以及 功能性残疾，除了更传统的参数，如 肾存活率和存活率本身。 这将是第一个系统的 在美国对患有SLE的西班牙裔人进行的一项研究， 不同种族的遗传和社会文化因素之间的相互作用 和少数民族的SLE患者。

A growing body of data suggests that genetic factors, particularly genes of the major histocompatibility complex, impact on the course and prognosis of rheumatic diseases. Likewise, recent work attests to the importance of socioeconomic factors in the outcome of these disorders. Systemic Lupus Erythematosus (SLE) is a disease of great variability whose prevalence, morbidity, and mortality have been found to be higher in minority groups. This proposal seeks to explore the factors underlying higher morbidity in minority groups with SLE by examining the relationship of socioeconomic, demographic, cultural, immunogenetic, and clinical variables to early outcome in an inception cohort study of Hispanic, African-American, and Caucasian SLE patients from 2 geographical areas (Houston, TX and Birmingham, AL). Since most genetic studies on SLE have focused on Caucasians of European ancestry, findings have been limited by linkage disequilibrium within this relatively homogeneous racial group. Therefore, HLA class II genotypes (HLA-DRB1, DRB3, DRB5, DQA1, DQB1 and DPB1 alleles) will be determined by oligotyping as well as gene dosage thereof, and class III C4 and C2 protein allotypes will be determined in each of 80 Hispanics, 80 African- American and 80 Caucasians consecutively enrolled into the study. The examination of SLE across different racial and ethnic groups not only allows us the opportunity to better determine the role of specific genes in the pathogenesis of SLE, but allows the unique opportunity to examine other factors differentially related to ethnicity - such as health care behavior, compliance, education, and comorbidities - to determine the interplay of genetic and socio-cultural factors in the outcome of SLE in both minority and non-minority groups. Patients with 5 years or less of disease duration will be recruited from the existing lupus registries at the University of Alabama at Birmingham (UAB) and the University of Texas Health Sciences Center (UTHSC) at Houston which are being expanded to insure complete case ascertainment. Hispanic patients will be recruited at UTHSC (and UT Medical Branch at Galveston) whereas African-American and Caucasian patients will be recruited at both UAB, and UTHSC. Outcome measures will be evaluated biannually for three years. The outcomes to be examined are sensitive to early change and include frequency and severity of flares, disease activity (SLAM) and severity (SLICC), and functional disability in addition to more traditional parameters such as renal survival and survival per se. This will be the first systematic study of Hispanics with SLE in the United States and the first to examine the interplay among genetic and socio-cultural factors in diverse racial and ethnic groups with SLE.