학술논문

Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian–European populations
Document Type
article
Source
Arthritis & Rheumatism. 64(11)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Health Sciences
Genetics
Autoimmune Disease
Clinical Research
Lupus
Kidney Disease
American Indian or Alaska Native
Inflammatory and immune system
Adolescent
Adult
Child
Female
Genetic Predisposition to Disease
Genotype
Humans
Indians
North American
Indians
South American
Lupus Erythematosus
Systemic
Lupus Nephritis
Male
Middle Aged
Morbidity
Prevalence
Risk Factors
Socioeconomic Factors
White People
Young Adult
Clinical Sciences
Immunology
Public Health and Health Services
Arthritis & Rheumatology
Clinical sciences
Language
Abstract
ObjectiveAmerican Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients.MethodsA total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).ResultsThe average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement.ConclusionIn general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.