Analysis of a Functional BTNL2 Polymorphism in Type 1 Diabetes, Rheumatoid Arthritis, and Systemic Lupus Erythematosus

Orozco, Gisela; Eerligh, Peter; Sánchez, Elena; Zhernakova, Alexandra; Roep, Bart O.; González-Gay, Miguel Á.; López–Nevot, Miguel A.; Callejas, José Luis; Hidalgo, Carmen; Pascual‐Salcedo, Dora; Balsa, Alejandro; González‐Escribano, María Francisca; Koeleman, Bobby P. C.; Martı́n, Javier

doi:10.1016/j.humimm.2006.02.003

Cited by 71 publications

(54 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…8,11 However, subsequent studies have showed inconsistent results on a sarcoidosis risk factor of BTNL2 rs2076530_A and its independent effect of HLA-DRB1. 12,13 In other diseases, such as type 1 diabetes (T1D), 14 rheumatoid arthritis (RA), 15 systemic lupus erythematosus (SLE), 14 multiple sclerosis (MS), 15 Graves'disease (GD), 16 chronic beryllium disease (CBD), 17 and ulcerative colitis (UC), 18 a significant association with BTNL2 polymorphisms appeared to be secondary to the primary HLA-DRB1 association because of its strong linkage disequilibrium (LD) with DRB1 alleles.…”

Section: Resultsmentioning

confidence: 99%

“…8,[11][12][13] This reflects the extensive linkage disequilibrium across the HLA region and the difficulties to assign primary associated locus within this genomic region. [14][15][16] Multivariable logistic regression analyses showed that BTNL2 effects are independent of human leukocyte antigen class II genes in Caucasians, but may interact antagonistically in African Americans. 11 In our study, strong LD was observed between DRB1* alleles (DRB1*08, DRB1*09, DRB1*11, DRB1*12, DRB1*14, DRB1*15) and BTNL2 rs2076530_A, particularly for DRB1*08:03 or the DRB1*09:01 allele and BTNL2 rs2076530_A.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Characterization and Susceptibility for Sarcoidosis in Japanese Patients: Risk Factors ofBTNL2Gene Polymorphisms and HLA Class II Alleles

Suzuki

Ôta

Meguro

et al. 2012

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic Characterization and Susceptibility for Sarcoidosis in Japanese Patients: Risk Factors ofBTNL2Gene Polymorphisms and HLA Class II Alleles

Suzuki

Ôta

Meguro

et al. 2012

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

“…A polymorphic variant affecting transcript splicing at the human BTNL2 locus has been linked by genetic analyses to inflammatory autoimmune conditions, including sarcoidosis, ulcerative colitis, and Crohn's disease (28)(29)(30). BTNL2 lies close to the highly polymorphic MHC class II HLA-DRB locus, a genomic region characterized by extensive and variable linkage disequilibrium, making it difficult to resolve genetic associations independently from those documented for MHC class II alleles (31,32).…”

Section: S K I N T 8 S K I N T 7 S K I N T 1 Skint4 Skint3 Skint9 Skint2mentioning

confidence: 99%

Regulation of Immunity by Butyrophilins

Rhodes

Reith

Trowsdale

2016

Annu. Rev. Immunol.

134

137

View full text Add to dashboard Cite

Butyrophilin molecules (commonly contracted to BTN), collectively take their name from the eponymous protein in cow's milk. They are considered to be members of the B7 family of costimulatory receptors, which includes B7.1 (CD80), B7.2 (CD86), and related molecules, such as PD-L1 (B7-H1, CD274), ICOS-L (CD275), and B7-H3 (CD276). These coreceptors modulate T cell responses upon antigen presentation by major histocompatibility complex and cognate αβ T cell receptor engagement. Molecules such as BTN3A1 (CD277), myelin oligodendrocyte glycoprotein, and mouse Skint1 and Btnl2, all members of the butyrophilin family, show greater structural and functional diversity than the canonical B7 receptors. Some butyrophilins mediate complex interactions between antigen-presenting cells and conventional αβ T cells, and others regulate the immune responses of specific γδ T cell subsets by mechanisms that have characteristics of both innate and adaptive immunity.

show abstract

“…Genomic mapping of disease loci identified a SNP (rs2076530) in the butyrophilin-like 2 gene (BTNL2) that increases the risk for sarcoidosis (23). polymorphisms in BTNL2 in linkage disequilibrium with hla-drb were related to other inflammatory diseases, all of which can be characterized by inappropriate t-cell activation (24)(25)(26). our previous study (16) showed that the T allele increased the transcription activity of BTN2A1 and the overexpression of BTN2A1 decreased the expression of elastin mrna and increased the mrna expression of matrix metallopeptidase 3 and interleukin 5. these observations suggest that the T allele of rs6929846 of BTN2A1 may accelerate vascular inflammation (16).…”

Section: Discussionmentioning

confidence: 99%

Association of a polymorphism of BTN2A1 with chronic kidney disease in individuals with or without hypertension or diabetes mellitus

Yoshida¹,

Kato

Oguri³

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. hypertension and diabetes mellitus are important risk factors for chronic kidney disease (cKd). We previously showed that the c→t polymorphism (rs6929846) of BTN2A1 was significantly associated with myocardial infarction. The purpose of the present study was to examine an association of rs6929846 of BTN2A1 with cKd in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of cKd in such individuals separately. the study population comprised 7,542 unrelated individuals, including 2,289 subjects with CKD [estimated glomerular filtration rate (eGFr) <60 ml/min/1.73 m 2 ] and 5,253 controls (eGFr ≥60 ml/min/1.73 m 2 ) with or without hypertension or diabetes mellitus. the chi-square test, a multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that the c→t polymorphism (rs6929846) of BTN2A1 was significantly associated with cKd in normotensive individuals, in diabetic individuals and in individuals with hypertension and diabetes mellitus, or without either condition, with the T allele representing a risk factor for CKD. Stratification of subjects based on hypertension or diabetes mellitus may thus be important in order to achieve personalized prevention of cKd with the use of genetic information. Introduction chronic kidney disease (cKd) is an important global public health problem because of its high morbidity in the general population. recent studies suggest that the risk for death is increased in individuals who have impaired renal function, but do not require dialysis, compared to those who have preserved renal function (1,2). disease prevention is an important strategy for reducing the overall burden of cKd and end-stage renal disease (ESRD), and the identification of markers for cKd risk is essential both for risk prediction and for potential intervention to reduce the chance of future cardiovascular complications (3).Several risk factors for progression of cKd have been proposed (4), with hypertension and diabetes mellitus having been recognized as important risk factors for cKd (5-7) as well as for coronary heart disease and stroke. in addition to these conventional risk factors, recent studies have shown the importance of genetic factors and of interactions between multiple genes and environmental factors in the development of cKd (8,9). although recent genome-wide association studies (GWaSs) (10-15) have implicated several loci and candidate genes in predisposition to cKd or ESrd in caucasians or african-american populations, the genes that contribute to genetic susceptibility to cKd in asian populations remain to be identified definitively. Gifu prefectural General medical center, Gifu; 8 department of Vascular biology, institute of brain Science, hirosaki university Graduate School of medicine, hirosaki; 9 department of Genomics for longevity and health, and 10 research team for Social participation and health promotion, tokyo metropolitan institute of Gero...

show abstract

Analysis of a Functional BTNL2 Polymorphism in Type 1 Diabetes, Rheumatoid Arthritis, and Systemic Lupus Erythematosus

Cited by 71 publications

References 20 publications

Genetic Characterization and Susceptibility for Sarcoidosis in Japanese Patients: Risk Factors ofBTNL2Gene Polymorphisms and HLA Class II Alleles

Genetic Characterization and Susceptibility for Sarcoidosis in Japanese Patients: Risk Factors ofBTNL2Gene Polymorphisms and HLA Class II Alleles

Regulation of Immunity by Butyrophilins

Association of a polymorphism of BTN2A1 with chronic kidney disease in individuals with or without hypertension or diabetes mellitus

Contact Info

Product

Resources

About