DataSheet_1_Favorable Genotypes of Type III Interferon Confer Risk of Dyslipidemia in the Population With Obesity.docx

BackgroundStudies have indicated that the chronic state of inflammation caused by obesity leads to dyslipidemia. However, how the polymorphisms involved in these inflammatory pathways affect the lipid metabolism in people with obesity is poorly understood. We investigated the associations of inflammation-related gene polymorphisms with dyslipidemia in individuals with obesity living in China.
MethodsThis case–control study in a population with obesity involved 194 individuals with dyslipidemia and 103 individuals without dyslipidemia. Anthropometric indices of obesity, fasting plasma glucose, blood pressure, blood lipids, and C-reactive protein were evaluated. The genes we tested were IL6 (interleukin 6), IL6R (interleukin 6 receptor), FOXP3 (forkhead box P3), TLR2 (toll-like receptor 2), TLR4 (toll-like receptor 4), IFNL3 (interferon lambda 3, formerly known as IL28B), and IFNL4 (interferon lambda 4, formerly known as IL29). Polymorphisms were genotyped using matrix-assisted laser desorption/ionization-time of flight mass spectrometry.
ResultsThere were significant differences in the allelic and genotype frequencies of IFNL3 (IL28B) rs12971396, rs8099917, rs11882871, rs12979860, rs4803217 between non-dyslipidemia and dyslipidemia groups in people with obesity. These single nucleotide polymorphisms (SNPs) of IFNL3 were highly linked (D′ and r > 0.90), so the result of one SNP could represent the result of other SNPs. For IFNL3 rs12971396, people with the homozygous genotype (the major group) carried a higher risk of dyslipidemia than people with the heterozygous genotype (P < 0.001, OR = 4.46, 95%CI, 1.95–10.22).
ConclusionsThe favorable genotypes of type III interferon, which have a beneficial role in anti-virus function, were associated with dyslipidemia in a Chinese population with obesity. Type III interferon could have a pathologic role and confer risk of dyslipidemia in people with obesity and chronic inflammation.

背景
已有研究表明，肥胖引发的慢性炎症状态会导致血脂异常。然而，目前对于这些炎症通路相关的基因多态性如何影响肥胖人群的脂质代谢，学界认知仍较为匮乏。本研究针对中国境内居住的肥胖人群，探讨了炎症相关基因多态性与血脂异常的关联。

方法
本病例对照研究纳入肥胖人群队列，其中血脂异常者194例，血脂正常者103例。检测指标包括肥胖相关人体测量学参数、空腹血糖、血压、血脂水平以及C反应蛋白。本次检测的基因包括：IL6（白细胞介素6，interleukin 6）、IL6R（白细胞介素6受体，interleukin 6 receptor）、FOXP3（叉头框P3，forkhead box P3）、TLR2（Toll样受体2，toll-like receptor 2）、TLR4（Toll样受体4，toll-like receptor 4）、IFNL3（Ⅲ型干扰素λ3，原称IL28B，interferon lambda 3, formerly known as IL28B）、IFNL4（Ⅲ型干扰素λ4，原称IL29，interferon lambda 4, formerly known as IL29）。采用基质辅助激光解吸电离飞行时间质谱（matrix-assisted laser desorption/ionization-time of flight mass spectrometry）进行基因多态性分型。

结果
在肥胖人群中，血脂异常组与血脂正常组的IFNL3（IL28B）rs12971396、rs8099917、rs11882871、rs12979860、rs4803217的等位基因频率与基因型频率均存在显著差异。上述IFNL3单核苷酸多态性（single nucleotide polymorphisms, SNPs）间存在高度连锁不平衡（D′与r>0.90），因此单个SNP的检测结果可代表其余SNP的结果。针对IFNL3 rs12971396，纯合基因型（野生型纯合子组）人群相较于杂合基因型人群，罹患血脂异常的风险更高（P<0.001，OR=4.46，95%CI：1.95~10.22）。

结论
在中国肥胖人群中，具备抗病毒有益功能的Ⅲ型干扰素优势基因型与血脂异常存在显著关联。本研究结果提示，Ⅲ型干扰素可能在肥胖合并慢性炎症人群中发挥病理作用，并增加其发生血脂异常的风险。