Klass Dietmar M, Lauer Nadine, Hay Birgit, Kratzer Wolfgang, Fuchs Michael
Department of Internal Medicine I, University Hospital Ulm, Germany.
Am J Gastroenterol. 2007 Nov;102(11):2482-7. doi: 10.1111/j.1572-0241.2007.01430.x. Epub 2007 Jul 19.
The beta3-adrenergic receptor (ADRB3) is a transmembrane receptor highly expressed in adipose tissue and thought to be involved in the regulation of lipolysis. ADRB3 is also highly expressed in gallbladder tissue where it may be involved in gallbladder contraction. Because polymorphisms of ADRB3 are present in populations with a high prevalence of gallstones (e.g., Pima-Indians, obese subjects), we hypothesized that known polymorphisms for ADRB3 (Trp64Arg) may represent an independent risk factor for gallstone disease.
The EMIL cross-sectional study investigated the health behavior and prevalence of chronic diseases in a small Southwestern German town of 12,475 inhabitants. From 3,893 randomly selected citizens 2,147 subjects were enrolled and screened for gallstones employing ultrasonography. Blood samples were drawn for biochemical analysis and isolation of genomic DNA. ADBR3 genotypes were determined by TaqMan SNP Assay.
We identified 171 (8%) gallstone carriers of whom 143 participated (46 male, 97 female), with a mean age of 51.4, and mean BMI of 29.3 kg/m2. For these subjects an age, gender and BMI matched partner without gallstones was recruited from the study population. Genotyping for ADRB3 revealed an Arg64 allele frequency of 5.9 versus 0.7% (HR = 11.9, P < 0.05) compared with controls.
Our results indicate that the ADRB3 Trp64Arg polymorphism is associated with gallstone disease thereby representing a genetic marker that identifies subjects at higher risk for gallstone formation.
β3-肾上腺素能受体（ADRB3）是一种在脂肪组织中高度表达的跨膜受体，被认为参与脂肪分解的调节。ADRB3在胆囊组织中也高度表达，可能参与胆囊收缩。由于ADRB3的多态性存在于胆结石患病率较高的人群中（如皮马印第安人、肥胖受试者），我们推测ADRB3已知的多态性（Trp64Arg）可能是胆结石疾病的一个独立危险因素。
EMIL横断面研究调查了德国西南部一个有12475名居民的小镇的健康行为和慢性病患病率。从3893名随机选择的公民中，招募了2147名受试者，采用超声检查筛选胆结石。采集血样进行生化分析并分离基因组DNA。通过TaqMan SNP分析确定ADBR3基因型。
我们鉴定出171名（8%）胆结石携带者，其中143名参与研究（46名男性，97名女性），平均年龄51.4岁，平均BMI为29.3kg/m²。从研究人群中为这些受试者招募了年龄、性别和BMI匹配的无胆结石伴侣。ADRB3基因分型显示，与对照组相比，Arg64等位基因频率为5.9%，而对照组为0.7%（HR=11.9，P<0.05）。
我们的结果表明，ADRB3 Trp64Arg多态性与胆结石疾病相关，因此是一种识别胆结石形成风险较高受试者的遗传标记。
