한국인 원형탈모증 환자에서 IL17A 및 IL17RA 유전자 다형성과 질병의 감수성에 관한 연구 Association between IL17A/IL17RA Gene Polymorphisms and Susceptibility to Alopecia Areata in Korean Population원문보기
원형 탈모증은 한국인 전체인구의 1% 이상에서 발병율을 보이는 원인미상의질환이다. 원형탈모증의 발생에 유전적인 배경이 중요한 것으로 인식되고 있으며, 근래에는 자가면역질환의 일종일 것으로 추측하고 있다. IL-17 은 건선, 류마티스 관절염, ...
원형 탈모증은 한국인 전체인구의 1% 이상에서 발병율을 보이는 원인미상의질환이다. 원형탈모증의 발생에 유전적인 배경이 중요한 것으로 인식되고 있으며, 근래에는 자가면역질환의 일종일 것으로 추측하고 있다. IL-17 은 건선, 류마티스 관절염, 다발성 경화증 등의 자가면역질환의 발병에 중요한 역할을 할것이라고 알려져있으나, 원형탈모증에서의 IL-17 과 IL-17RA 의 역할에 대한 연구는 보고되지 않았다. 따라서 저자들은 IL17A 및 IL17RA 유전자의 다형성이 대표적인 자가면역 질환인 원형탈모증의 발현에 유의한 영향이 있는지 조사해보고자 하였다. 이에 저자들은 원형탈모증 환자 238명과 건강한 대조군 270명을 대상으로 IL17A, IL17RA 유전자의 각각 두가지와 네가지 single nucleotide polymorphims (SNPs)를 선정하여 genotype 분포, allele 빈도를 비교 분석하였다. 염기서열 분석 결과, IL17A 의 SNP 는 환자군과 대조군 사이에 유의한 차이가 없었으며, IL17RA의 SNPs 중 두가지 (rs879575 와 rs879577) 는 환자군과 대조군 사이에서 유의한 차이를 보였다. IL17RA 유전자의 rs2229151은 30세 이전에 발병한 조기발병형과 30세 이후에 발병한 후기 발병형 원형탈모 환자군간의 유의한 차이가 관찰되었다. 또한 IL17A 유전자의 두가지 SNPs 인 rs2275913 and rs3819024 는 판형의 원형탈모와 전두탈모또는 범발성탈모간에 유의한 차이를 보였다. 두 유전자 모두 SNPs가 LD 블록을 이루지는 않았다. 이로써 IL17A 또는 IL17RA 유전자 다형성은 원형탈모증의 발병 또는 표현형과 상호 연관성이 있음을 추정해볼 수 있다.
원형 탈모증은 한국인 전체인구의 1% 이상에서 발병율을 보이는 원인미상의질환이다. 원형탈모증의 발생에 유전적인 배경이 중요한 것으로 인식되고 있으며, 근래에는 자가면역질환의 일종일 것으로 추측하고 있다. IL-17 은 건선, 류마티스 관절염, 다발성 경화증 등의 자가면역질환의 발병에 중요한 역할을 할것이라고 알려져있으나, 원형탈모증에서의 IL-17 과 IL-17RA 의 역할에 대한 연구는 보고되지 않았다. 따라서 저자들은 IL17A 및 IL17RA 유전자의 다형성이 대표적인 자가면역 질환인 원형탈모증의 발현에 유의한 영향이 있는지 조사해보고자 하였다. 이에 저자들은 원형탈모증 환자 238명과 건강한 대조군 270명을 대상으로 IL17A, IL17RA 유전자의 각각 두가지와 네가지 single nucleotide polymorphims (SNPs)를 선정하여 genotype 분포, allele 빈도를 비교 분석하였다. 염기서열 분석 결과, IL17A 의 SNP 는 환자군과 대조군 사이에 유의한 차이가 없었으며, IL17RA의 SNPs 중 두가지 (rs879575 와 rs879577) 는 환자군과 대조군 사이에서 유의한 차이를 보였다. IL17RA 유전자의 rs2229151은 30세 이전에 발병한 조기발병형과 30세 이후에 발병한 후기 발병형 원형탈모 환자군간의 유의한 차이가 관찰되었다. 또한 IL17A 유전자의 두가지 SNPs 인 rs2275913 and rs3819024 는 판형의 원형탈모와 전두탈모또는 범발성탈모간에 유의한 차이를 보였다. 두 유전자 모두 SNPs가 LD 블록을 이루지는 않았다. 이로써 IL17A 또는 IL17RA 유전자 다형성은 원형탈모증의 발병 또는 표현형과 상호 연관성이 있음을 추정해볼 수 있다.
Alopecia areata (AA) is an organ-specific autoimmune disease characterized by T-cell infiltrates and cytokine production around anagen-stage hair follicles. There is evidence for loss of immune privilege coupled with T cell mediated attack of hair follicle autoantigens. The role of T helper (Th)1 an...
Alopecia areata (AA) is an organ-specific autoimmune disease characterized by T-cell infiltrates and cytokine production around anagen-stage hair follicles. There is evidence for loss of immune privilege coupled with T cell mediated attack of hair follicle autoantigens. The role of T helper (Th)1 and Th2 cytokines in the pathogenesis of AA have not been fully established. The evidence for the role of cytokines and T-cells in AA includes the beneficial effects of systemic steroids and calcineurin inhibitors. Autoimmune diseases result from many factors, including the interaction of the genetic background of the immune system with the environment. That AA could be linked to genetic factors is supported by the fact that in 10% to 20% of the cases the patient's family reported a family history of this disease. It is probable that AA and other autoimmune diseases are polygenic, with multiple potential routes of genetic susceptibility. Many studies have been done on the linkages of various genes to AA. But the most extensive work has been done on the linkages with the HLA hapolotypes. Less extensive work has also been done on immune response and other genes. In addition to HLA genes, there are known genetic polymorphisms in cytokine receptors and antigen-processing molecules. In study of cytokine mRNA levels in AA before and after treatment with the contact allergen diphenylcyclopropenone(DCP), after DCP treatment, the interferon (IFN)-γ expression was reduced, whereas mRNA expression of interleukin (IL)-2, IL-8, IL-10, and tumor necrosis factor (TNF)-α was increased. IL-4 is found in sera from patients with AA and sera from C3H/HeJ AA mice, but is lower than levels found in sera from patients with atopic dermatitis. A predominance of Th1 cytokines (IL-2, IL-12 and IFN-γ) has been found previously in AA skin lesions from patients with AA and C3H⁄HeJ AA mice, and were higher in the sera from all patients with AA than in the controls. In addition, IL-4 was detected in a small percentage of the AA samples but was undetectable in controls. IL-6 and IL-10 levels were also greater in patients with AA than controls, but the difference was not significant. Although the balance of Th1 and Th2 cytokines may play a role in AA, other cytokines may also to be involved. In particular, higher levels of IL-1ra and IL-8 in patients with AA than in controls has been known. Th1 serum cytokines, IL-8 and IL-1ra are associated with AA and may be involved in its pathogenesis. Several studies in the late 1990s implicated IL-17 in the pathogenesis of autoimmunity. Elevated IL-17 levels were found in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis patients, though it was not clear from these studies how important a role it might play in disease pathogenesis. The IL-17 cytokine family consists of six members: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, and IL-17F. The best characterized member of this family is IL-17A, its expression facilitating the definition of a newly discovered lineage of CD4+ effector T cells, the Th17 subset16-20. IL-17A became a major focus of research only recently, after a novel IL-17A-producing Th cell lineage (Th17) was discovered. IL-17A is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), though it was not clear from these studies how important a role it might play in disease pathogenesis. The receptor for IL-17A, which is further on referred to as IL-17R, is abundantly expressed by all cells of the immune system, and stimulation of various cell types with IL-17 can induce the expression of other cytokines such as IL-1β, TNF and IL-6, and the chemokines IL-8 and macrophage inflammatory protein 1 (MIP-1). In contrast to the restricted set of cells that produce IL-17, mRNA of the IL-17R is expressed ubiquitously in many cell types and shares no homology with any other cytokine receptor family. The role of IL-17 on the pathogenesis of AA has not be studied yet, however, we can suggest that IL-17 can be associated with AA like other autoimmune diseases. The purpose of this study is to determine whether variation in IL17A/IL17RA gene contributes to the risk of AA in Korean population. Two single nucleotide polymorphisms (SNPs) of IL17A gene and a total of 4 SNPs of IL17RA gene are tested in this study.
Alopecia areata (AA) is an organ-specific autoimmune disease characterized by T-cell infiltrates and cytokine production around anagen-stage hair follicles. There is evidence for loss of immune privilege coupled with T cell mediated attack of hair follicle autoantigens. The role of T helper (Th)1 and Th2 cytokines in the pathogenesis of AA have not been fully established. The evidence for the role of cytokines and T-cells in AA includes the beneficial effects of systemic steroids and calcineurin inhibitors. Autoimmune diseases result from many factors, including the interaction of the genetic background of the immune system with the environment. That AA could be linked to genetic factors is supported by the fact that in 10% to 20% of the cases the patient's family reported a family history of this disease. It is probable that AA and other autoimmune diseases are polygenic, with multiple potential routes of genetic susceptibility. Many studies have been done on the linkages of various genes to AA. But the most extensive work has been done on the linkages with the HLA hapolotypes. Less extensive work has also been done on immune response and other genes. In addition to HLA genes, there are known genetic polymorphisms in cytokine receptors and antigen-processing molecules. In study of cytokine mRNA levels in AA before and after treatment with the contact allergen diphenylcyclopropenone(DCP), after DCP treatment, the interferon (IFN)-γ expression was reduced, whereas mRNA expression of interleukin (IL)-2, IL-8, IL-10, and tumor necrosis factor (TNF)-α was increased. IL-4 is found in sera from patients with AA and sera from C3H/HeJ AA mice, but is lower than levels found in sera from patients with atopic dermatitis. A predominance of Th1 cytokines (IL-2, IL-12 and IFN-γ) has been found previously in AA skin lesions from patients with AA and C3H⁄HeJ AA mice, and were higher in the sera from all patients with AA than in the controls. In addition, IL-4 was detected in a small percentage of the AA samples but was undetectable in controls. IL-6 and IL-10 levels were also greater in patients with AA than controls, but the difference was not significant. Although the balance of Th1 and Th2 cytokines may play a role in AA, other cytokines may also to be involved. In particular, higher levels of IL-1ra and IL-8 in patients with AA than in controls has been known. Th1 serum cytokines, IL-8 and IL-1ra are associated with AA and may be involved in its pathogenesis. Several studies in the late 1990s implicated IL-17 in the pathogenesis of autoimmunity. Elevated IL-17 levels were found in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis patients, though it was not clear from these studies how important a role it might play in disease pathogenesis. The IL-17 cytokine family consists of six members: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, and IL-17F. The best characterized member of this family is IL-17A, its expression facilitating the definition of a newly discovered lineage of CD4+ effector T cells, the Th17 subset16-20. IL-17A became a major focus of research only recently, after a novel IL-17A-producing Th cell lineage (Th17) was discovered. IL-17A is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), though it was not clear from these studies how important a role it might play in disease pathogenesis. The receptor for IL-17A, which is further on referred to as IL-17R, is abundantly expressed by all cells of the immune system, and stimulation of various cell types with IL-17 can induce the expression of other cytokines such as IL-1β, TNF and IL-6, and the chemokines IL-8 and macrophage inflammatory protein 1 (MIP-1). In contrast to the restricted set of cells that produce IL-17, mRNA of the IL-17R is expressed ubiquitously in many cell types and shares no homology with any other cytokine receptor family. The role of IL-17 on the pathogenesis of AA has not be studied yet, however, we can suggest that IL-17 can be associated with AA like other autoimmune diseases. The purpose of this study is to determine whether variation in IL17A/IL17RA gene contributes to the risk of AA in Korean population. Two single nucleotide polymorphisms (SNPs) of IL17A gene and a total of 4 SNPs of IL17RA gene are tested in this study.
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