Department of Internal Medicine, Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
BMC Med Genet. 2013 May 20;14:54. doi: 10.1186/1471-2350-14-54.
Hormone sensitive lipase (HSL) promoter (LIPE-60 C > G) polymorphism has been found to be involved in hepatic steatosis, obesity, diabetes and dyslipidemia. The precise interactions between these risk factors and genetic susceptibility that may affect non-alcoholic fatty liver disease (NAFLD) are still not fully determined.
A cross-sectional study was conducted in 1056 men. To avoid the confounding effect of plasma glucose, the study population was classified into normal glucose tolerance (NGT, n = 729) and glucose intolerance (GI, n = 299) groups. NAFLD was diagnosed by abdominal ultrasound after ruling out any history of alcohol abuse. A multivariate regression model was used to estimate the impact of these factors on NAFLD.
In the NGT group, subjects with NAFLD often have complicated metabolic abnormalities. The coexistence of NAFLD and GI has been demonstrated to have a synergistic effect raising BMI, serum insulin and HOMA-insulin resistance (HOMA-IR). BMI and adipose-insulin resistance (Adipo-IR), but not HOMA-IR, significantly contributed to a greater risk of developing NAFLD. Serum triglyceride was significantly up-regulated in men with the (CG + GG) genotype of HSL promoter polymorphism, NAFLD and Adiopo-IR in sequence.
Adipo-IR, rather than HOMA-IR, appears to be a consistent insulin resistance index in the study of NAFLD. G allele of the HSL promoter polymorphism may contribute the greatest impact raising serum triglyceride in a state of glucose intolerance.
激素敏感脂肪酶（HSL）启动子（LIPE-60C>G）多态性与肝脂肪变性、肥胖、糖尿病和血脂异常有关。这些危险因素与遗传易感性之间的确切相互作用可能影响非酒精性脂肪性肝病（NAFLD），但尚未完全确定。
对 1056 名男性进行了横断面研究。为了避免血糖的混杂影响，将研究人群分为正常糖耐量（NGT，n=729）和糖耐量受损（GI，n=299）两组。在排除任何酒精滥用史后，通过腹部超声诊断 NAFLD。使用多元回归模型来估计这些因素对 NAFLD 的影响。
在 NGT 组中，患有 NAFLD 的患者通常存在复杂的代谢异常。已经证明，NAFLD 与 GI 的共存具有协同作用，会导致 BMI、血清胰岛素和 HOMA 胰岛素抵抗（HOMA-IR）升高。BMI 和脂肪胰岛素抵抗（Adipo-IR），而不是 HOMA-IR，显著增加了发生 NAFLD 的风险。HSL 启动子多态性 CG+GG 基因型、NAFLD 和 Adiopo-IR 依次出现的男性血清甘油三酯水平显著升高。
在 NAFLD 的研究中，Adipo-IR 似乎比 HOMA-IR 更能反映一致性胰岛素抵抗。HSL 启动子多态性的 G 等位基因可能在葡萄糖耐量受损的情况下对升高血清甘油三酯产生最大影响。
