已经证明维生素D受体(VDR),维生素D(VD)代谢的关键基因,可能通过调节非酒精性脂肪性肝病(NAFLD)的水平及其生物学效应来影响NAFLD的发生发展。
为了研究血清VD水平的影响,VDR变化,结合VDRSNP和环境行为因素对NAFLD风险的影响。
南京某社区共纳入3023名受试者,包括1120例NAFLD病例和1903例对照。测定血清25(OH)D3水平,并对VDR基因中的八个单核苷酸多态性(SNP)进行基因分型。
Logistic回归分析表明,VD充足和VD不足与NAFLD的低风险显着相关(所有P<0.05;所有P趋势<0.05,以位点剂量方式)。在调整了性别和年龄后,VDRrs2228570-A和rs11168287-A等位基因均降低了NAFLD的风险(在显性模型中,所有PFDR=0.136;P趋势=0.039,以基因座剂量方式的联合作用)。两个有利等位基因的保护作用在≤40岁的受试者中更为明显,非高血压,非高血糖和非低高密度脂蛋白胆固醇(均P<0.05)。VDRSNP和运动时间联合评估NAFLD风险的受试者工作曲线下面积略高于仅包括运动时间或不包括运动时间(均P<0.05)。
高血清VD水平和VDR变异(rs2228570-A和rs11168287-A)可能导致中国汉族人群NAFLD的低风险。纳入VDRSNP和运动时间可以提高NAFLD风险评估的效率。这可能为早期筛查和预防NAFLD提供新的视角。
It has been demonstrated that vitamin D receptor (VDR), a key gene in the metabolism of vitamin D (VD), may affect the development of Non-alcoholic fatty liver disease (NAFLD) by regulating VD level and its biological effects.
To investigate the effects of serum VD level, VDR variation, and a combination of VDR SNP and environmental behavior factor on the risk of NAFLD.
A total of 3023 subjects from a community in Nanjing were enrolled, including 1120 NAFLD cases and 1903 controls. Serum 25(OH)D3 levels were measured and eight single nucleotide polymorphisms (SNPs) in VDR gene were genotyped.
Logistic regression analyses indicated that VD sufficiency and VD insufficiency were significantly associated with a low risk of NAFLD (all P<0.05; all P trend <0.05, in a locus-dosage manner). After adjusting for gender and age, VDR rs2228570-A and rs11168287-A alleles were all reduced the risk of NAFLD (all P FDR=0.136, in dominant model; P trend =0.039, combined effects in a locus-dosage manner). The protective effects of two favorable alleles were more evident among subjects ≤40 years, non-hypertension, non-hyperglycemia and non-low high density lipoprotein-cholesterol (all P<0.05). The area under the receiver operating curve of the combination of VDR SNP and exercise time for assessing NAFLD risk was slightly higher than that of only including exercise time or neither (all P<0.05).
High serum VD levels and VDR variants (rs2228570-A and rs11168287-A) might contribute to a low risk of NAFLD in Chinese Han population. The inclusion of VDR SNP and exercise time could improve the efficiency in assessment of NAFLD risk, which might provide a novel perspective for early screening and preventing NAFLD.