Uribe, A. G., McGwin, G. Jr, Reveille, J. D. & Alarcon, G. S. What have we learned from a 10-year experience with the LUMINA (Lupus in Minorities; nature vs. Nurture) cohort? Where are we heading? Autoimmun. Rev. 3, 321-329
ABSTRACT Recently, there has been an awareness of the variable phenotypic expression of numerous disorders between individuals from different ethnicities, systemic lupus erythematosus (SLE) one of them. These disparities probably arise from the interaction between genetic and non-genetic (environmental, socioeconomic-demographic, cultural and behavioral) factors. To delineate the influence of these factors on SLE outcome, we established a multiethnic (Hispanic, African American and Caucasian) United States (US) early cohort (<5 years disease duration). Ten years later, interesting data have emerged from the LUMINA (Lupus in Minorities: Nature vs. nurture) cohort. For example, African Americans and Hispanics from Texas have a more severe disease than Caucasians and Hispanics from Puerto Rico. Lack of private insurance, acute SLE onset, expression of HLA-DRB1*01 (DR1) and C4A*3 alleles were associated with higher disease activity, whereas age, the number of American College of Rheumatology criteria met, disease activity, corticosteroid use and abnormal illness behaviors were consistent predictors of damage. In turn, damage and poverty were found to predict mortality. We now plan to apply new approaches (genetic admixture) to deconfound the complex interaction between genetic and non-genetic factors influencing SLE outcome. These data may have impact on the development of policies aimed at eliminating health disparities in the US.
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- "SNPs rs9271366 (the most significant signal in the present study) and rs2071349 are both located inside the HLA class II region that has been consistently associated with SLE in European, East Asian and African American populations (Fernando et al. 2007; Han et al. 2009; Hom et al. 2008; Reveille et al. 1998; Rioux et al. 2009b; Uribe et al. 2004). It is noteworthy that a recent GWAS found the rs9271366 SNP to be associated with SLE in Chinese Han subjects at genome-wide significance (Han et al. 2009). "
ABSTRACT: The major histocompatibility complex (MHC) on chromosome 6p21 is a key contributor to the genetic basis of systemic lupus erythematosus (SLE). Although SLE affects African Americans disproportionately compared to European Americans, there has been no comprehensive analysis of the MHC region in relationship to SLE in African Americans. We conducted a screening of the MHC region for 1,536 single nucleotide polymorphisms (SNPs) and the deletion of the C4A gene in a SLE case-control study (380 cases, 765 age-matched controls) nested within the prospective Black Women's Health Study. We also genotyped 1,509 ancestral informative markers throughout the genome to estimate European ancestry to control for population stratification due to population admixture. The most strongly associated SNP with SLE was the rs9271366 (odds ratio, OR = 1.70, p = 5.6 × 10(-5)) near the HLA-DRB1 gene. Conditional haplotype analysis revealed three other SNPs, rs204890 (OR = 1.86, p = 1.2 × 10(-4)), rs2071349 (OR = 1.53, p = 1.0 × 10(-3)), and rs2844580 (OR = 1.43, p = 1.3 × 10(-3)), to be associated with SLE independent of the rs9271366 SNP. In univariate analysis, the OR for the C4A deletion was 1.38, p = 0.075, but after simultaneous adjustment for the other four SNPs the odds ratio was 1.01, p = 0.98. A genotype score combining the four newly identified SNPs showed an additive risk according to the number of high-risk alleles (OR = 1.67 per high-risk allele, p < 0.0001). Our strongest signal, the rs9271366 SNP, was also associated with higher risk of SLE in a previous Chinese genome-wide association study (GWAS). In addition, two SNPs found in a GWAS of European ancestry women were confirmed in our study, indicating that African Americans share some genetic risk factors for SLE with European and Chinese subjects. In summary, we found four independent signals in the MHC region associated with risk of SLE in African American women.Human Genetics 06/2011; 130(6):807-15. DOI:10.1007/s00439-011-1045-2 · 4.52 Impact Factor
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ABSTRACT: Despite increased severity of lupus in blacks, including more frequent neuropsychiatric manifestations, there is sparse data on neuropsychologic function in black patients with lupus. Neuropsychologic functioning and health-related variables were examined among blacks (n = 34) and whites (n = 14) fulfilling American College of Rheumatology criteria for systemic lupus erythematosus. Blacks and whites performed comparably on measures of verbal and visual memory, working memory, and motor speed after controlling for estimates of premorbid cognitive ability. Blacks trended towards poorer performance on specific attention/processing speed measures. Pain, fatigue, depression, anxiety, physical and emotional well-being were unrelated to ethnicity. Blacks exhibited a trend towards greater impairment of physical functioning. Ethnicity-related differences in overall damage, noncognitive neuropsychiatric manifestations, and prevalence of nephritis revealed greater severity among blacks. Initial differences in premorbid cognitive function possibly contribute to disparate clinical outcomes, including a greater proportion of blacks exhibiting subnormal neurocognitive performance. Blacks evidencing lower premorbid ability may be at greater vulnerability for poorer functional outcomes (eg, coping skills, medical compliance and employment) if they experience disease-related cognitive dysfunction.JCR Journal of Clinical Rheumatology 11/2005; 11(5):250-6. DOI:10.1097/01.rhu.0000182149.67967.cc · 1.25 Impact Factor
- Arthritis & Rheumatology 11/2005; 53(5):781-4. DOI:10.1002/art.21458 · 7.87 Impact Factor