Hangzhou Normal University, Hangzhou, Zhejiang, China.
Department of Endocrinology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
Adv Ther. 2019 Apr;36(4):880-895. doi: 10.1007/s12325-019-00902-z. Epub 2019 Feb 28.
Haptoglobin (Hp) genotypes were reported as an independent risk factor for metabolic diseases. This study aimed to investigate the association between Hp gene polymorphism and the severity of nonalcoholic fatty liver disease (NAFLD).
A total of 441 subjects (NAFLD group, n = 272; healthy control, n = 169) were recruited, and their clinical biochemical parameters were measured in all subjects. Haptoglobin genotyping was performed using genomic DNA extracted from peripheral blood leukocytes. Among the NAFLD group, 107 patients underwent liver biopsy, and histology was evaluated by a pathologist on the basis of the CRN scoring system.
NAFLD patients had much lower frequency of Hp 1-1 genotype and higher frequency of Hp 2-2 than healthy controls (0.4% vs 9.5%, 55.8% vs 47.9%, P < 0.001). NAFLD patients with Hp 2-2 genotype had much higher levels of body mass index (BMI), total cholesterol (TC), liver enzymes, ferritin, and controlled attenuation parameter (CAP) values than non-Hp 2-2 genotype (P < 0.05). In histology, patients with nonalcoholic steatohepatitis (NASH) had higher frequency of Hp 2-2 genotype than non-NASH patients (71.3% vs 22.2%, P < 0.001); patients with significant fibrosis had higher frequency of Hp 2-2 genotype (78.3% vs 54.8%, P < 0.05) than no/mild fibrosis patients. NAFLD patients with Hp 2-2 genotype had higher proportion with higher steatosis scores, lobular inflammation scores, ballooning scores, NAFLD activity scores (NAS), and fibrosis stages (P < 0.05 for all) than Hp 2-2 groups. Furthermore, Hp 2-2 genotype was independently associated with NASH (OR = 5.985, P < 0.05) and significant fibrosis (OR = 6.584, P < 0.05).
Hp 2-2 genotype is closely associated with the severity of NAFLD.
触珠蛋白（Hp）基因型被报道为代谢疾病的独立危险因素。本研究旨在探讨 Hp 基因多态性与非酒精性脂肪性肝病（NAFLD）严重程度的关系。
共招募 441 例受试者（NAFLD 组，n=272；健康对照组，n=169），所有受试者均测量其临床生化参数。通过提取外周血白细胞中的基因组 DNA 进行触珠蛋白基因分型。在 NAFLD 组中，107 例患者进行了肝活检，病理学家根据 CRN 评分系统对组织学进行评估。
与健康对照组相比，NAFLD 患者 Hp 1-1 基因型的频率明显降低，而 Hp 2-2 基因型的频率明显升高（0.4%比 9.5%，55.8%比 47.9%，P<0.001）。与非 Hp 2-2 基因型相比，Hp 2-2 基因型的 NAFLD 患者的体重指数（BMI）、总胆固醇（TC）、肝酶、铁蛋白和受控衰减参数（CAP）值更高（P<0.05）。在组织学上，非酒精性脂肪性肝炎（NASH）患者的 Hp 2-2 基因型频率明显高于非 NASH 患者（71.3%比 22.2%，P<0.001）；有显著纤维化的患者的 Hp 2-2 基因型频率明显高于无/轻度纤维化的患者（78.3%比 54.8%，P<0.05）。与 Hp 2-2 基因型组相比，Hp 2-2 基因型的 NAFLD 患者具有更高比例的更高脂肪变性评分、肝小叶炎症评分、气球样变评分、NAFLD 活动评分（NAS）和纤维化分期（所有 P<0.05）。此外，Hp 2-2 基因型与 NASH（OR=5.985，P<0.05）和显著纤维化（OR=6.584，P<0.05）独立相关。
Hp 2-2 基因型与 NAFLD 的严重程度密切相关。
