The C-terminal binding protein 2 (CTBP2) gene (translational isoforms: CTBP2-L/S, RIBEYE) had been identified by a cross-trait analysis of genome-wide association studies for anorexia nervosa (AN) and body mass index (BMI). Here, we did a mutation analysis in CTBP2 by performing polymerase chain reactions with subsequent Sanger-sequencing to identify variants relevant for AN and body weight regulation and ensued functional studies. Analysis of the coding regions of CTBP2 in 462 female patients with AN (acute or recovered), 490 children and adolescents with severe obesity, 445 healthy-lean adult individuals and 168 healthy adult individuals with normal body weight detected 24 variants located in the specific exon of RIBEYE. In the initial analysis, three of these were rare non-synonymous variants (NSVs) detected heterozygously in patients with AN (p.Arg72Trp - rs146900874; p.Val289Met -rs375685611 and p.Gly362Arg - rs202010294). Four NSVs and one heterozygous frameshift variant were exclusively detected in children and adolescents with severe obesity (p.Pro53Ser - rs150867595; p.Gln175ArgfsTer45 - rs141864737; p.Leu310Val - rs769811964; p.Pro397Ala - rs76134089 and p.Pro402Ser - rs113477585). Ribeye mRNA was detected in mouse hypothalamus. No effect of fasting or overfeeding on murine hypothalamic Ribeye expression was determined. Yet, increased Ribeye expression was detected in hypothalami of leptin-treated Lep^ob/ob mice. This increase was not related to reduced food intake and leptin-induced weight loss. We detected rare and frequent variants in the RIBEYE specific exon in both patients with AN and in children and adolescents with severe obesity. Our data suggest RIBEYE as a relevant gene for weight regulation.

C 端结合蛋白 2 （CTBP2） 基因 （翻译亚型：CTBP2-L/S、RIBEYE） 已通过神经性厌食症 （AN） 和体重指数 （BMI） 的全基因组关联研究的交叉性状分析确定。在这里，我们通过进行聚合酶链反应和随后的 Sanger 测序来鉴定与 AN 和体重调节相关的变异，从而对 CTBP2 进行突变分析，并随后进行功能研究。对 462 名女性 AN 患者 （急性或恢复期） 、490 名严重肥胖儿童和青少年、445 名健康瘦成人个体和 168 名体重正常的健康成人个体的 CTBP2 编码区分析，检测到 24 个变异位于 RIBEYE 的特定外显子中。在初步分析中，其中三种是在 AN 患者中杂合检测到的罕见非同义变异 （NSV） （p.Arg72Trp - rs146900874;p.Val289Met -rs375685611 和 p.Gly362Arg - rs202010294）。在患有严重肥胖的儿童和青少年中仅检测到 4 个 NSV 和 1 个杂合移码变体 （p.Pro53Ser - rs150867595;p.Gln175ArgfsTer45 - rs141864737;p.Leu310Val - rs769811964;p.Pro397Ala - rs76134089 和 p.Pro402Ser - rs113477585）。在小鼠下丘脑中检测到 Ribeye mRNA。未确定禁食或过量喂养对小鼠下丘脑肋眼表达的影响。然而，在瘦素处理的 Lep^ob/ob 小鼠的下丘脑中检测到 Ribeye 表达增加。这种增加与食物摄入量减少和瘦素诱导的体重减轻无关。我们在 AN 患者和严重肥胖的儿童和青少年中检测到 RIBEYE 特异性外显子的罕见和频繁变异。 我们的数据表明 RIBEYE 是体重调节的相关基因。