Association of -2548 G/A Polymorphism of Leptin Gene with Cholesterol Gallstones_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Hongwei ¹ , WANG Fei ¹ , SONG Shaohua ¹ , SHEN Feng ¹ , ZHANG Xiaowen ² ,  ZHOU Wenbo ¹

1.Department of Hepatobiliary Surgery, Affiliated Dongfeng Hospital, Yunyang Medical College, Shiyan 442000, Hubei Province, China;;
2.The Second Department of General Surgery, The Second Affiliated Hospital of Kunming Medical College, Kunming 650101, Yunnan Province, China;

Corresponding author：

ZHOU Wenbo, Email: zwbmail@yahoo.com.cn

Keywords：

Gallstones; Leptin; Gene polymorphism

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ObjectiveTo explore the relationship between the -2548 G/A functional polymorphism in the 5′ promoter region of the leptin gene and gallstones. Methods　The -2548 G/A polymorphisms of leptin gene were determined by polymerase chain reactionrestriction fragment length polymorphism technology (PCRRFLP) in 118 patients with cholesterol gallstones and 53 normal control subjects. Then the allele and genotype distribution were studied. Results The distribution of leptin2458 G/A in two groups was statistically significantly different: the genotype frequency of AA+GA of patients in gallstone group was higher than that in control group (χ2=4.251, P=0.039). AA+AG genotype had 2.813 times greater risk for gallstone disease compared with GG genotype (OR=2.813, 95% CI=1.020-7.757). Allele frequency distribution in the two groups was different: the allele frequency of A of patients in gallstone group was higher than that in control group (χ2=5.791, P=0.016). The risk of gallstone disease in the A alleles carriers was 1.777 times as higher as the carriers of G alleles (OR=1.777, 95% CI=1.110-2.844). ConclusionThe -2548 G/A polymorphism in the 5′ promoter region of leptin gene is significantly correlated with the gallstones. The A alleles of leptin may be a genetic factor which contributes to individual susceptibility for gallstone, while the G alleles of leptin may be a genetic factor that prevents people from gallstone.

Citation： WU Hongwei ,WANG Fei,SONG Shaohua,SHEN Feng,ZHANG Xiaowen,ZHOU Wenbo. Association of -2548 G/A Polymorphism of Leptin Gene with Cholesterol Gallstones. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(1): 63-66. doi: Copy

1.	李哲夫, 陈孝平. 胆固醇胆石成因的研究进展 [J]. 中国普通外科杂志, 2007, 16(2): 170172.
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6.	Mammès O, Betoulle D, Aubert R, et al. Novel polymorphisms in the 5′ region of the LEP gene: association with leptin levels and response to lowcalorie diet in human obesity [J]. Diabetes, 1998, 47(3): 487489.
7.	Mammès O, Betoulle D, Aubert R, et al. Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight [J]. Ann Hum Genet, 2000, 64(Pt 5): 391394.
8.	Van der Lende T, Te Pas MF, Veerkamp RF, et al. Leptin gene polymorphisms and their phenotypic associations [J]. Vitam Horm, 2005, 71: 373404.
9.	Hoffstedt J, Eriksson P, MottaguiTabar S, et al. A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin [J]. Horm Metab Res, 2002, 34(7): 355359.
10.	Woods CM, Mawe GM, Shaffer EA, et al. Effects of bioactive agents on biliary motor function [J]. Curr Gastroenterol Rep, 2003, 5(2): 154159.
11.	Goldblatt MI, SwartzeBasile DA, Svatek CL, et al. Decreased gallbladder response in leptindeficient obese mice [J]. J Gastrointest Surg, 2002, 6(3): 438442.
12.	MéndezSánchez N, González V, KingMartínez AC, et al. Plasma leptin and the cholesterol saturation of bile are correlated in obese women after weight loss [J]. J Nutr, 2002, 132(8): 21952198.
13.	Hyogo H, Roy S, Paigen B, et al. Leptin promotes biliary cholesterol elimination during weight loss in ob/ob mice by regulating the enterohepatic circulation of bile salts [J]. J Biol Chem, 2002, 277(37): 3411734124.
14.	Tobe K, Suzuki R, Aoyama M, et al. Increased expression of the sterol regulatory elementbinding protein1 gene in insulin receptor substrate 2-/- mouse liver [J]. J Biol Chem, 2001, 276(42): 3833738340.
15.	雷正明, 曾道炳, 陈跃, 等. 瘦素、胆囊收缩素、血脂与胆石类型关系探讨 [J]. 中华肝胆外科杂志, 2007, 13(4): 220223.

1. 李哲夫, 陈孝平. 胆固醇胆石成因的研究进展 [J]. 中国普通外科杂志, 2007, 16(2): 170172.
2. 赵燕, 姚有贵. 胆固醇7α羟化酶基因多态性与胆固醇结石病关系的研究 [J]. 中国普外基础与临床杂志, 2010, 17(1): 6063.
3. 姚有贵, 马明坤, 蒲道深, 等. 载脂蛋白AⅠCⅢAⅣ基因簇XmnⅠ、MspⅠ位点多态性与胆固醇结石病关系的研究 [J]. 中国普外基础与临床杂志, 2007, 14(3): 287291.
4. Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue [J]. Nature, 2002, 372(6505): 425432.
5. 张红梅, 陈璐璐. 瘦素与胆结石 [J]. 临床肝胆病杂志, 2004, 20(1): 6163.
6. Mammès O, Betoulle D, Aubert R, et al. Novel polymorphisms in the 5′ region of the LEP gene: association with leptin levels and response to lowcalorie diet in human obesity [J]. Diabetes, 1998, 47(3): 487489.
7. Mammès O, Betoulle D, Aubert R, et al. Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight [J]. Ann Hum Genet, 2000, 64(Pt 5): 391394.
8. Van der Lende T, Te Pas MF, Veerkamp RF, et al. Leptin gene polymorphisms and their phenotypic associations [J]. Vitam Horm, 2005, 71: 373404.
9. Hoffstedt J, Eriksson P, MottaguiTabar S, et al. A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin [J]. Horm Metab Res, 2002, 34(7): 355359.
10. Woods CM, Mawe GM, Shaffer EA, et al. Effects of bioactive agents on biliary motor function [J]. Curr Gastroenterol Rep, 2003, 5(2): 154159.
11. Goldblatt MI, SwartzeBasile DA, Svatek CL, et al. Decreased gallbladder response in leptindeficient obese mice [J]. J Gastrointest Surg, 2002, 6(3): 438442.
12. MéndezSánchez N, González V, KingMartínez AC, et al. Plasma leptin and the cholesterol saturation of bile are correlated in obese women after weight loss [J]. J Nutr, 2002, 132(8): 21952198.
13. Hyogo H, Roy S, Paigen B, et al. Leptin promotes biliary cholesterol elimination during weight loss in ob/ob mice by regulating the enterohepatic circulation of bile salts [J]. J Biol Chem, 2002, 277(37): 3411734124.
14. Tobe K, Suzuki R, Aoyama M, et al. Increased expression of the sterol regulatory elementbinding protein1 gene in insulin receptor substrate 2-/- mouse liver [J]. J Biol Chem, 2001, 276(42): 3833738340.
15. 雷正明, 曾道炳, 陈跃, 等. 瘦素、胆囊收缩素、血脂与胆石类型关系探讨 [J]. 中华肝胆外科杂志, 2007, 13(4): 220223.

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Association of -2548 G/A Polymorphism of Leptin Gene with Cholesterol Gallstones

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