Association of Killer Cell Immunoglobulin-Like Receptors and Their HLA-Ligands with Type 1 Diabetes Among South Indian Population.

IF 2.9 4区医学 Q3 IMMUNOLOGY

Immunological Investigations Pub Date : 2023-04-01 DOI:10.1080/08820139.2023.2165940

Nagarajan Gunavathy, Arthur Asirvatham, Ayyappan Chitra, Mariakuttikan Jayalakshmi

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引用次数: 0

Abstract

Background: Type 1 diabetes (T1D) is a multifactorial autoimmune disease, involving strong genetic components with familial predisposition. Killer cell immunoglobulin-like receptors (KIRs) found on the surface of NK cells have ligands of human leukocyte antigen (HLA) class I that are associated with T1D. The present study evaluates the influence of KIR genes and their HLA-ligands in the aetiology of T1D among the South Indian population.

Methods: A total of 125 T1D patients, along with their parents (n = 126) and siblings (n = 52) were recruited. PCR-based genotyping was performed for KIR genes and HLA class I ligands. The gene frequencies were compared between patients and siblings/parents. Linkage-disequilibrium (LD) analysis was performed to assess the genetic association between KIR gene pairs.

Results: The results show significant differences in HLA-ligands of KIR genes between patients and parents. The HLA-C1C1 homozygosity was found to be a predisposing risk factor, and HLA-C1C2 heterozygosity was protective towards T1D along with either the activating KIR2DS2 or inhibitory KIRs 2DL1, 2DL2, 2DL3. However, the frequency of inhibitory KIR3DL1 significantly increased in the presence of HLA-B Bw4 Ile80 in parents when compared to patients showing a protective effect on T1D. Two pairs of KIR genes, 2DS4-3DL1 and 2DS1-2DL5, showed strong LD in patients, siblings and parents.

Conclusion: The KIR-HLA ligand combinations have a significant effect on T1D aetiology among the South Indian population. This study defines a pattern for family-based association studies with genotypic information about KIR genes and their HLA-ligands, providing the first evidence towards T1D among the South Indian population.

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南印度人群中杀伤细胞免疫球蛋白样受体及其hla配体与1型糖尿病的关系

背景:1型糖尿病(T1D)是一种多因素自身免疫性疾病，涉及强烈的遗传成分和家族易感性。NK细胞表面的杀伤细胞免疫球蛋白样受体(KIRs)具有与T1D相关的人白细胞抗原(HLA) I类配体。本研究评估了KIR基因及其hla配体在南印度人群T1D病因学中的影响。方法:共招募125例T1D患者及其父母(n = 126)和兄弟姐妹(n = 52)。对KIR基因和HLA I类配体进行pcr分型。比较了患者和兄弟姐妹/父母之间的基因频率。采用连锁不平衡分析(link- disequilibrium, LD)评估KIR基因对之间的遗传关联。结果:患者与父母在KIR基因hla配体上存在显著差异。HLA-C1C1纯合性是T1D的易感危险因素，HLA-C1C2杂合性对T1D具有保护作用，无论是激活KIR2DS2还是抑制kirs2dl1, 2DL2, 2DL3。然而，与对T1D有保护作用的患者相比，在父母中存在HLA-B Bw4 Ile80时，抑制性KIR3DL1的频率显著增加。两对KIR基因2DS4-3DL1和2DS1-2DL5在患者、兄弟姐妹和父母中表现出强烈的LD。结论:KIR-HLA配体组合对南印度人群T1D病因有显著影响。本研究定义了一种基于家族的与KIR基因及其hla配体基因型信息相关的研究模式，为南印度人群中的T1D提供了第一个证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunological Investigations 医学-免疫学

CiteScore

5.50

自引率

7.10%

发文量

审稿时长

3 months

期刊介绍： Disseminating immunological developments on a worldwide basis, Immunological Investigations encompasses all facets of fundamental and applied immunology, including immunohematology and the study of allergies. This journal provides information presented in the form of original research articles and book reviews, giving a truly in-depth examination of the latest advances in molecular and cellular immunology.