Supplementary Material for: The Combined Effects of Genetic Variation in the CNDP1 and CNDP2 Genes and Dietary Carbohydrate and Carotene Intake on Obesity Risk

<b><i>Background/Aims:</i></b> It is possible that carnosinase (CNDP1) and cellular nonspecific dipeptidase (CNDP2) have important roles in protecting cells and tissues against the damage of oxidative stress. Oxidative stress and subsequent inflammation are key factors in the development of common chronic metabolic diseases, such as obesity. We aimed to investigate the combined effects of genetic variations in <i>CNDP1</i> and <i>CNDP2</i> and dietary carbohydrate and carotene intake on obesity risk. <b><i>Methods:</i></b> A total of 1,059 Japanese men were randomly selected from participants who visited a medical center for routine medical checkups. We analyzed the relationships between the genotypes of 4 single-nucleotide polymorphisms (SNPs) (rs12605520, rs7244647, rs4891558, and rs17089368) in the <i>CNDP1/CNDP2 </i>locus and body mass index or prevalence of obesity/overweight taking into account dietary carbohydrate and carotene intake. <b><i>Results:</i></b> We found that 2 SNPs (rs7244647 in <i>CNDP1</i> and rs4891558 in <i>CNDP2</i>) were associated with obesity risk. In addition, these associations were observed only in the group with high carbohydrate and low carotene intake but not in the group with low carbohydrate and high carotene intake. <b><i>Conclusions:</i></b> Our findings indicate that the combination of genetic variations in <i>CNDP1 </i>and<i> CNDP2</i> and dietary carbohydrate/carotene intake modulate obesity risk.

**背景与目的：** 肌肽酶（CNDP1）与细胞非特异性二肽酶（CNDP2）或可在保护细胞及组织免受氧化应激损伤中发挥重要作用。氧化应激及其继发的炎症反应，是肥胖等常见慢性代谢性疾病发生发展的关键危险因素。本研究旨在探讨CNDP1与CNDP2基因变异、膳食碳水化合物及胡萝卜素摄入对肥胖风险的联合影响。

**方法：** 本研究从前往某医疗中心接受常规体检的受试者中，随机纳入1059名日本男性。本研究分析了CNDP1/CNDP2基因位点上4个单核苷酸多态性（single-nucleotide polymorphisms, SNPs，即rs12605520、rs7244647、rs4891558及rs17089368）的基因型与体质量指数、肥胖/超重患病率之间的关联，并综合考虑了膳食碳水化合物与胡萝卜素摄入情况。

**结果：** 本研究发现，2个单核苷酸多态性位点（CNDP1基因上的rs7244647与CNDP2基因上的rs4891558）与肥胖风险存在显著关联。此外，上述关联仅在高碳水化合物、低胡萝卜素摄入的亚组中得以观察到，而在低碳水化合物、高胡萝卜素摄入的亚组中未发现此类关联。

**结论：** 本研究结果表明，CNDP1与CNDP2的基因变异、膳食碳水化合物及胡萝卜素摄入的联合作用，可调节肥胖风险。