Sex-specific analysis in Behcet's disease reveals higher genetic risk in male patients

被引：21

作者：

Jo, Yun Gun ^{[1
]}

Ortiz-Fernandez, Lourdes ^{[1
]}

Coit, Patrick ^{[1
]}

Yilmaz, Vuslat ^{[2
]}

Yentur, Sibel P. ^{[2
]}

Alibaz-Oner, Fatma ^{[3
]}

Aksu, Kenan ^{[4
]}

Erken, Eren ^{[5
]}

Duzgun, Nursen ^{[6
]}

Keser, Gokhan ^{[4
]}

Cefle, Ayse ^{[7
]}

Yazici, Ayten ^{[7
]}

Ergen, Andac ^{[8
]}

Alpsoy, Erkan ^{[9
]}

Salvarani, Carlo ^{[10
,11
]}

Kisacik, Bunyamin ^{[12
]}

Koetter, Ina ^{[13
,14
]}

Henes, Joerg ^{[15
,16
]}

Cinar, Muhammet ^{[17
]}

Schaefer, Arne ^{[18
]}

Nohutcu, Rahime M. ^{[19
]}

Takeuchi, Fujio ^{[20
]}

Harihara, Shinji ^{[21
]}

Kaburaki, Toshikatsu ^{[22
]}

Messedi, Meriam ^{[23
]}

Song, Yeong-Wook ^{[24
,25
]}

Kasifoglu, Timucin ^{[26
]}

Martin, Javier ^{[27
]}

Gonzalez Escribano, Maria Francisca ^{[28
]}

Saruhan-Direskeneli, Guher ^{[2
]}

Direskeneli, Haner ^{[3
]}

Sawalha, Amr H. ^{[1
,29
,30
,31
]}

机构：

[1] Univ Pittsburgh, Dept Pediat, Div Rheumatol, Pittsburgh, PA 15260 USA

[2] Istanbul Univ, Istanbul Med Fac, Dept Physiol, Istanbul, Turkey

[3] Marmara Univ, Sch Med, Dept Internal Med, Div Rheumatol, Istanbul, Turkey

[4] Ege Univ, Sch Med, Dept Internal Med, Div Rheumatol, Izmir, Turkey

[5] Cukurova Univ, Sch Med, Dept Internal Med, Div Rheumatol, Adana, Turkey

[6] Ankara Univ, Sch Med, Dept Internal Med, Div Rheumatol, Ankara, Turkey

[7] Kocaeli Univ, Sch Med, Dept Internal Med, Div Rheumatol, Kocaeli, Turkey

[8] Okmeydan Res & Educ Hosp, Ophthalmol Clin, Istanbul, Turkey

[9] Akdeniz Univ, Sch Med, Dept Dermatol & Venereol, Antalya, Turkey

[10] Azienda USL IRCCS Reggio Emilia, Reggio Emilia, Italy

[11] Univ Modena & Reggio Emilia, Modena, Italy

[12] Gaziantep Univ, Fac Med, Dept Internal Med, Div Rheumatol, Gaziantep, Turkey

[13] Univ Hosp Eppendorf, Div Rheumatol & Syst Inflammatory Dis, Hamburg, Germany

[14] Clin Rheumatol & Immunol, Bad Bramstedt, Germany

[15] Univ Hosp Tuebingen, Ctr Interdisciplinary Rheumatol Immunol & Autoinf, Tubingen, Germany

[16] Univ Hosp Tuebingen, Internal Med Hematol Oncol Rheumatol & Immunol 2, Tubingen, Germany

[17] Univ Hlth Sci Turkey, Gulhane Fac Med, Dept Internal Med, Div Rheumatol, Ankara, Turkey

[18] Charite Univ Med Berlin, Inst Dent & Craniofacial Sci, Dept Periodontol Oral Med & Oral Surg, Berlin, Germany

[19] Hacettepe Univ Sihhiye, Fac Dent, Dept Periodontol, Ankara, Turkey

[20] Univ Shizuoka, Sch Pharmaceut Sci, Shizuoka, Japan

[21] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Tokyo, Japan

[22] Jichi Med Univ, Dept Ophthalmol, Saitama Med Ctr, Saitama, Japan

[23] Univ Sfax, Fac Med Sfax, Res Lab Mol Bases Human Dis, 12ES17, Sfax, Tunisia

[24] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea

[25] Seoul Natl Univ, Coll Med, Med Res Ctr, Seoul, South Korea

[26] Osmangazi Univ, Sch Med, Dept Internal Med, Div Rheumatol, Eskisehir, Turkey

[27] PTS Granada, Inst Parasitol & Biomed Lopez Neyra, IPBLN CSIC, Granada, Spain

[28] Univ Seville, Serv Inmunol, IBiS, Hosp Univ Virgen Rocio,CSIC, Ibis, Spain

[29] Univ Pittsburgh, Dept Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA

[30] Univ Pittsburgh, Lupus Ctr Excellence, Sch Med, Pittsburgh, PA USA

[31] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA

来源：

JOURNAL OF AUTOIMMUNITY | 2022年 / 132卷

基金：

美国国家卫生研究院;

关键词：

Behcet's disease; Sex-bias; Genetics; HLA class I; GWAS; MHC; GENOME-WIDE ASSOCIATION; MHC CLASS-I; SUSCEPTIBILITY LOCI; IDENTIFICATION; GENOTYPE; HLA-B-ASTERISK-51; IL23R-IL12RB2; PREVALENCE; HAPLOTYPES; EPISTASIS;

D O I：

10.1016/j.jaut.2022.102882

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Objectives: Behcet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behcet's disease. Methods: A total of 1762 male and 1216 female patients with Behcet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behcet's disease was calculated and compared between male and female patients. Results: Genetic association analysis comparing male to female patients with Behcet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 x 10-8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behcet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behcet's disease was observed in male patients in HLA-B/ MICA (rs116799036, OR = 1.45, P = 1.95 x 10-8), HLA-C (rs12525170, OR = 1.46, P = 5.66 x 10-7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. Conclusions: Male patients with Behcet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behcet's disease.

引用

页数：7

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