scholarly journals Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yong-Fei Wang ◽  
Yan Zhang ◽  
Zhiming Lin ◽  
Huoru Zhang ◽  
Ting-You Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Genome Wide Association Study ◽  
Age Of Onset ◽  
Treatment Options ◽  
Human Leukocyte ◽  
Risk Scores ◽  
Systemic Lupus ◽  
Disease Manifestation ◽  
A Genome

AbstractSystemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.

scholarly journals Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity that may underly population disparities in this disease

2020 ◽  
Author(s):  
Yong-Fei Wang ◽  
Yan Zhang ◽  
Zhiming Lin ◽  
Huoru Zhang ◽  
Ting-You Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Genome Wide Association Study ◽  
Age Of Onset ◽  
Treatment Options ◽  
Risk Scores ◽  
Systemic Lupus ◽  
Disease Manifestation ◽  
Chinese Populations ◽  
A Genome

AbstractSystemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underly the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertook a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture were identified. Nine disease loci showed clear ancestral group heterogeneity and implicated antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores performed significantly better when trained on matched ancestral data sets. These analyses help to reveal the genetic bases for disparities in SLE among ancestral groups.

scholarly journals A genome wide association study of systemic lupus erythematosus (SLE) by SLEGEN, the International SLE Genetics Consortium.

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
John B. Harley ◽  
Marta E Alarcon‐Riquelme ◽  
Lindsey A Criswell ◽  
Chaim O. Jacob ◽  
Robert P. Kimberly ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Association Study ◽  
Lupus Erythematosus ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Systemic Lupus ◽  
Genome Wide ◽  
A Genome

scholarly journals Molecular Analysis of HLA-DR and Their Association with Systemic Lupus Erythematosus

2017 ◽  
Vol 42 (3) ◽  
pp. 111-119
Author(s):  
Sumaiya Khatun ◽  
Ahmed Abu Saleh ◽  
Chandan Kumar Roy ◽  
Shafinaj Khan ◽  
Suparna Pal ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Hla Antigens ◽  
Human Leukocyte ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Hla Dr ◽  
Genetic And Environmental Factors ◽  
Bangladeshi Population

Systemic lupus erythematosus (SLE) is an autoimmune disease that develops within a complex network of genetic and immunologic factors. Both genetic and environmental factors strongly influence the      development of SLE. But genetic factors are more important both in determining the overall susceptibility to SLE and in influencing immunologic heterogenecity in affected subjects. Now it is accepted that major histocompatibility complex (MHC) genes particularly HLA (Human leukocyte antigen) class II constitute a part of the genetic factor for susceptibility to develop SLE. To determine the association of HLA-DR antigens with SLE, this case-control study was conducted over a period of twelve months from March 2013 in Dhaka. Buccal swabs for HLA-DR typing were collected from 46 SLE cases and 46 age and sex matched unrelated healthy controls. HLA-DR typing was carried out by polymerase chain        reaction (PCR) with sequence specific primers. Among 46 cases, female versus male ration was 22: 1 and mean age at study entry was 27.05 ± 8.17 years, ranging from 12.5 – 45 years. A total of 10      (HLA-DR1 to DR10) HLA antigens were determined in both cases and controls. The most frequent HLA-DR observed among cases was DR2 (86.96%) followed by DR7 (41.30%). When compared with healthy controls, the HLA-DR2 was significantly associated with SLE (p ?0.05, RR: 4.6914, 95% CI: 1.658 to 13.267). No other HLA-DR had significant association with SLE. No association of HLA-DR was observed with age of onset of disease among SLE cases. Results of the study reveal that HLA-DR2 gene is a risk factor for development of SLE in Bangladeshi population.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

Expression of human leukocyte antigen-G in systemic lupus erythematosus

2008 ◽  
Vol 69 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Silvia Rosado ◽  
Gema Perez-Chacon ◽  
Susana Mellor-Pita ◽  
Inmaculada Sanchez-Vegazo ◽  
Carmen Bellas-Menendez ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Human Leukocyte Antigen ◽  
Lupus Erythematosus ◽  
Human Leukocyte ◽  
Systemic Lupus ◽  
Leukocyte Antigen ◽  
Human Leukocyte Antigen G

scholarly journals Positive Selection Affects the Expression of Systemic Lupus Erythematosus Associated Loci in Human Populations

2021 ◽  
Author(s):  
Victoria Oberreiter ◽  
Tobias Goellner ◽  
David L. Morris ◽  
Helmut Schaschl
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Positive Selection ◽  
Lupus Erythematosus ◽  
Lifestyle Changes ◽  
Genetic Ancestry ◽  
Selection Function ◽  
Human Populations ◽  
Systemic Lupus ◽  
A Genome

Abstract Background: Systemic lupus erythematosus (SLE) shows marked population-specific disparities in disease prevalence, including substantial variation in manifestations and complications according to genetic ancestry. Several recent studies suggest that a substantial proportion of variation of gene expression shows genetic ancestry-associated differences in gene regulation on immune responses. Positive selection may act in a population-specific manner on expression quantitative trait loci (eQTLs) and thereby contributes to the difference in the differences of SLE prevalence and manifestation in human populations. We tested the hypothesises that some of the identified SLE risk polymorphisms display pleiotropic effects or polygenicity driven by positive selection. We performed a genome-wide scan for recent positive selection by using integrated Haplotype Score (iHS) statistics in different human populations. In addition, we estimated the timing of beneficial mutations to understand what possible selective pressures drive positive selection at SLE-associated loci. Results: We identified several SLE risk loci that are population-specifically under positive selection. Almost all SNPs that are under positive selection function as cis-eQTLs in different tissue types. We determined that adaptive eQTLs affect the expression of fewer genes than non-adaptive eQTLs, suggesting a limited range of effect of an eQTL at SLE risk sites that show signatures of positive selection. Furthermore, some positively selected SNPs are located in transcription factor binding sequences. The timing of positive selection for the studied loci suggests that both environmental and recent lifestyle changes during as well as after the Neolithic Transition may have become selectively effective. We propose a novel link between positively selected eQTLs at a certain SLE risk locus in Europeans and a physiological pathway not previously considered in SLE.Conclusions: We conclude that population-specific adaptive eQTLs contribute to the observed variation in specific manifestations and complications of SLE in different ethnicities. Our results suggest also that human populations adapt more rapidly to environmental and lifestyle stimuli via modification of gene expression without having to alter the genetic code.

scholarly journals Cutaneous Manifestations of “Lupus”: Systemic Lupus Erythematosus and Beyond

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Elizabeth E. Cooper ◽  
Catherine E. Pisano ◽  
Samantha C. Shapiro
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Cutaneous Lupus Erythematosus ◽  
Laboratory Studies ◽  
Systemic Lupus ◽  
Cutaneous Manifestations ◽  
Distinct Disease ◽  
Cutaneous Lupus

Lupus, Latin for “wolf,” is a term used to describe many dermatologic conditions, some of which are related to underlying systemic lupus erythematosus, while others are distinct disease processes. Cutaneous lupus erythematosus includes a wide array of visible skin manifestations and can progress to systemic lupus erythematosus in some cases. Cutaneous lupus can be subdivided into three main categories: acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus. Physical exam, laboratory studies, and histopathology enable differentiation of cutaneous lupus subtypes. This differentiation is paramount as the subtype of cutaneous lupus informs upon treatment, disease monitoring, and prognostication. This review outlines the different cutaneous manifestations of lupus erythematosus and provides an update on both topical and systemic treatment options for these patients. Other conditions that utilize the term “lupus” but are not cutaneous lupus erythematosus are also discussed.

scholarly journals Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yuan-yuan Qi ◽  
Xin-ran Liu ◽  
Ying-xin He ◽  
Min Zhou ◽  
Xiang-hui Ning ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Genetic Association ◽  
Lupus Erythematosus ◽  
Genome Wide Association Study ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Chinese Populations ◽  
Genetic Heritability

A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of telomere. Given that only a small portion of the genetic heritability of SLE has been explained so far, we aimed to identify novel loci in telomere-related genes responsible for SLE susceptibility in Chinese populations. We performed a comprehensive genetic association analysis of SLE with telomere-related genes. To identify functional significance, we analyzed the publicly available HaploReg v4.1 and RegulomeDB databases. Differential gene expression analysis was also performed using ArrayExpress. A novel signal of PINX1 rs6984094 was identified ( P discovery = 4.13 × 10 − 2 , OR = 0.58 , 95% CI 0.35-0.98) and successfully replicated ( P replication = 5.73 × 10 − 3 , OR = 0.45 , 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the PINX1 rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of PINX1 mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between PINX1 (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations.

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