De Luis D A, González Sagrado M, Aller R, Conde R, Izaola O, de la Fuente B, Primo D
Instituto de Endocrinología y Nutrición, Facultad de Medicina, Universidad de Valladolid, Valladolid, España.
Nutr Hosp. 2011 Mar-Apr;26(2):317-22. doi: 10.1590/S0212-16112011000200012.
A intragenic biallelic polymorphism (1359 G/A) of the CB1 gene resulting in the substitution of the G to A at nucleotide position 1359 in codon 435 (Thr), was reported as a common polymorphism in Caucasian populations. Intervention studies with this polymorphism have not been realized.
We decided to investigate the role of the polymorphism (G1359A) of CB1 receptor gene on adipocytokines response and weight loss secondary to a lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients.
A population of 94 patients with obesity was analyzed. Before and after 3 months on a hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for the combined G1359A and A1359A as a group and wild type G1359G as second group, with a dominant model.
Forty seven patients (50%) had the genotype G1359G (wild type group) and 47 (50%) patients G1359A (41 patients, 43.6%) or A1359A (6 patients, 6.4%) (mutant type group) had the genotype. In wild and mutant type groups, weight, body mass index, fat mass, waist circumference and systolic blood pressure decreased. In mutant type group, resistin (4.15 ± 1.7 ng/ml vs. 3.90 ± 2.1 ng/ml: P < 0.05), leptin (78.4 ± 69 ng/ml vs 66.2 ± 32 ng/ml: P < 0.05) and IL-6 (1.40 ± 1.9 pg/ml vs 0.81 ± 1.5 pg/ml: P < 0.05) levels decreased after dietary treatment.
The novel finding of this study is the association of the mutant allele (A1359) with a decrease of resistin, leptin and interleukin-6 secondary to weight loss.
据报道，CB1基因的一种基因内双等位基因多态性（1359G/A）导致密码子435（苏氨酸）的第1359位核苷酸由G替换为A，这是白种人群中的一种常见多态性。尚未开展针对这种多态性的干预研究。
我们决定研究CB1受体基因多态性（G1359A）对肥胖患者脂肪细胞因子反应以及生活方式改变（地中海低热量饮食和运动）所致体重减轻的作用。
对94例肥胖患者进行了分析。在低热量饮食3个月前后，进行了人体测量评估、营养摄入评估和生化分析。采用显性模型，将G1359A和A1359A合并为一组，野生型G1359G作为第二组进行统计分析。
47例患者（50%）具有G1359G基因型（野生型组），47例患者（50%）具有G1359A基因型（41例患者，43.6%）或A1359A基因型（6例患者，6.4%）（突变型组）。野生型组和突变型组的体重、体重指数、脂肪量、腰围和收缩压均下降。在突变型组中，饮食治疗后抵抗素（4.15±1.7 ng/ml对3.90±2.1 ng/ml：P<0.05）、瘦素（78.4±69 ng/ml对66.2±32 ng/ml：P<0.05）和IL-6（1.40±1.9 pg/ml对0.81±1.5 pg/ml：P<0.05）水平下降。
本研究的新发现是突变等位基因（A1359）与体重减轻后抵抗素、瘦素和白细胞介素-6的降低有关。
