中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (11): 1839-1844.doi: 10.4103/1673-5374.194756

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

人类白细胞抗原二类等位基因能否作为2型糖尿病患者周围神经病变的遗传标志物?

  

  • 出版日期:2016-11-30 发布日期:2016-11-30
  • 基金资助:
    伊朗哈马丹医科大学研究技术基金资助

HLA class II alleles and risk for peripheral neuropathy in type 2 diabetes patients

Ahmad Marzban1, Javad Kiani1, Mehrdad Hajilooi2, Hamzeh Rezaei2, Zohreh Kahramfar1, Ghasem Solgi2, 3, *   

  1. 1 Division of Endocrinology, Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran 2 Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran 3 Psoriasis Research Center, Department of Dermatology, Farshchian Hospital, Hamadan University of Medical Sciences, Hamadan, Iran
  • Online:2016-11-30 Published:2016-11-30
  • Contact: Ghasem Solgi, Ph.D., gh.solgi@umsha.ac.ir.
  • Supported by:
    This study was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences of Iran, No .9208072467.

摘要:

人类白细胞抗原(HLA)遗传变异性对糖尿病周围神经病变的潜在影响尚未得到证实。研究旨在确定HLA二类等位基因与2型糖尿病周围神经病变的关系。共106例2型糖尿病患者纳入研究,其中49例患有周围神经病变,57例无周围神经病变;同时100名种族、性别、年龄与之匹配的健康对照者也被纳入研究。应用序列特异引物引导的PCR反应法检测HLA-DRB1和 DQB1基因型。患有周围神经病变的2型糖尿病患者HLA-DRB1*10和 DRB1*12等位基因频率明显高于健康对照者;HLA-DQB1*02等位基因和HLA-DRB1*07–DQB1*02单倍体与2型糖尿病患者周围神经病变发展的危险因素下降有关;同时,相较于轻中度神经病变者,有严重神经病变的患者DRB1*07和DQB1*02基因频率更高;患者与健康对照者DRB1和 DQB1等位基因及单倍体分布无明显差异。这些结果说明,HLA-DQB1*02等位基因和HLA-DRB1*07-DQB1*02单倍体对于2型糖尿病周围神经病变的发展起保护作用,HLA基因型变异也许可作为2型糖尿病周围神经病变预测和管理的遗传标志。 

orcid: 0000-0001-8929-5658 (Ghasem Solgi)

关键词: 神经再生, HLA-DRB1, HLA-DQB1, 等位基因, 基因型, 单倍体, 基因变异, 2型糖尿病, 围神经病变

Abstract: The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. Tis study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. Te distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our fndings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Terefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.

Key words: nerve regeneration, HLA-DRB1, HLA-DQB1, alleles, genotypes, haplotypes, peripheral neuropathy, type 2 diabetes, neural regeneration