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印度南部泰米尔人群中IL-12B和IL-23R基因变异与银屑病风险关联的研究。

Investigation of association of the IL-12B and IL-23R genetic variations with psoriatic risk in a South Indian Tamil cohort.

作者信息

Indhumathi S, Rajappa Medha, Chandrashekar Laxmisha, Ananthanarayanan P H, Thappa D M, Negi V S

机构信息

Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

出版信息

Hum Immunol. 2016 Jan;77(1):54-62. doi: 10.1016/j.humimm.2015.10.006. Epub 2015 Oct 20.

Abstract

BACKGROUND

Psoriasis is a T-cell mediated chronic systemic inflammatory skin disease. Emerging evidences suggest the interleukin (IL)-12B and IL-23R genes encoding the common p40 subunit of IL-12 and IL-23 are the key cytokines in T-helper (Th)1 and Th17 differentiation and function. Certain allelic variants of these genes significantly influence the risk of psoriasis. Hence we undertook to study the association of IL-12B and IL-23R gene polymorphisms with disease susceptibility in South Indian Tamil patients with psoriasis.

METHODS

360 psoriatics and 360 healthy controls were included in this case control study. IL-12B gene (rs3212227) and IL-23R gene (rs2201841, rs10889677 and rs11805303) polymorphisms were typed by using TaqMan 5'allele discrimination assay and cytokine levels were assayed by ELISA.

RESULTS

We observed that the patients carrying the risk genotypes of IL-12B (rs3212227) and IL-23R (rs2201841) conferred an increased susceptibility to psoriasis. We did not find any significant association between IL-23R (rs10889677 and rs11805303) gene polymorphisms and psoriasis risk in South Indian Tamil population. We did not observe any significant difference in haplotypes between the psoriasis cases and controls. We observed a significant increase in the mean IL-23 levels in psoriatics and the higher levels of IL-23 were found in the minor variant genotype CC when compared with that of heterozygous CT and major variant TT genotypes of rs2201841. Individual genotypes of rs10889677 and rs11805303 and IL-12 (rs3212227) were not significantly associated with their plasma levels.

CONCLUSION

Our results suggest that IL-12B (rs3212227) and IL-23R (rs2201841) polymorphisms confer increased risk of psoriasis in our ethnic South Indian Tamils.

摘要

背景

银屑病是一种由T细胞介导的慢性全身性炎症性皮肤病。新出现的证据表明,编码白细胞介素(IL)-12和IL-23共同p40亚基的IL-12B和IL-23R基因是辅助性T(Th)1和Th17分化及功能的关键细胞因子。这些基因的某些等位基因变体显著影响银屑病的发病风险。因此,我们着手研究IL-12B和IL-23R基因多态性与南印度泰米尔族银屑病患者疾病易感性之间的关联。

方法

本病例对照研究纳入了360例银屑病患者和360例健康对照。采用TaqMan 5'等位基因鉴别分析法对IL-12B基因(rs3212227)和IL-23R基因(rs2201841、rs10889677和rs11805303)的多态性进行分型,并采用酶联免疫吸附测定法检测细胞因子水平。

结果

我们观察到,携带IL-12B(rs3212227)和IL-23R(rs2201841)风险基因型的患者患银屑病的易感性增加。在南印度泰米尔族人群中未发现IL-23R(rs10889677和rs11805303)基因多态性与银屑病风险之间存在显著关联。我们未观察到银屑病病例与对照之间单倍型有任何显著差异。我们观察到银屑病患者的平均IL-23水平显著升高,与rs2201841的杂合子CT和主要变体TT基因型相比,次要变体基因型CC中的IL-23水平更高。rs10889677和rs11805303以及IL-12(rs3212227)的个体基因型与其血浆水平无显著关联。

结论

我们的结果表明,在我们南印度泰米尔族人群中,IL-12B(rs3212227)和IL-23R(rs2201841)多态性会增加患银屑病的风险。

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