Karolinska Institutet, Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
J Intern Med. 2010 Sep;268(3):279-85. doi: 10.1111/j.1365-2796.2010.02249.x. Epub 2010 Apr 28.
Recently, variants of the hepatocanalicular cholesterol hemitransporters ABCG5/8 were linked to gallstone disease; ABCG8 D19H in Caucasians and ABCG5 Q604E in Chinese. We investigated these polymorphisms in Swedish twins by merging the Swedish Twin Registry with the Hospital Discharge and Causes of Death Registries for gallstone disease-related diagnoses.
All monozygotic (MZ) twins with gallstone disease alive in the Stockholm area were invited to participate. Gallstone disease was defined by entry in all above mentioned registries, questionnaire or abdominal ultrasound.
ABCG5 Q604E and ABCG8 D19H genotyping was performed in 24 unique MZ and eight dizygotic (DZ) twins from concordant pairs. Screening of the TwinGene database for gallstone disease resulted in an additional 20 concordant MZ and 54 twins from concordant DZ pairs. We included 109 concordantly stone-free MZ and 126 stone-free independent DZ twins as controls.
Amongst the 341 twins, 20.8% carried at least one D19H allele as compared to 9.4% of stone-free controls. The association analysis showed that D19H positivity significantly increased the risk of gallstone disease [odds ratio (OR), 2.54; 95% confidence interval (CI), 1.33-4.82; P = 0.004]. We also found a trend for a positive association between gallstone disease and the Q604E variant (OR, 1.47; 95% CI, 1.00-2.16; P = 0.052).
Twins carrying a heterozygous or homozygous ABCG8 D19H genotype have a significantly increased risk of gallstone disease. Our study confirms the ABCG8 D19H genotype as a major risk factor for gallstone disease.
最近，肝细胞管胆固醇半转运体 ABCG5/8 的变异体与胆石病有关；白种人 ABCG8 D19H 和中国人 ABCG5 Q604E。我们通过将瑞典双胞胎登记处与住院和死因登记处合并，对瑞典双胞胎进行了这些多态性研究，以进行胆石病相关诊断。
所有在斯德哥尔摩地区患有胆石病的同卵（MZ）双胞胎都被邀请参加。胆石病的定义是通过上述所有登记处、问卷调查或腹部超声进入。
在 24 对独特的 MZ 和 8 对异卵（DZ）双胞胎中进行了 ABCG5 Q604E 和 ABCG8 D19H 基因分型。对 TwinGene 数据库进行胆石病筛查，结果又有 20 对 MZ 双胞胎和 54 对 DZ 双胞胎的结果一致。我们纳入了 109 对胆石病患者和 126 对胆石病患者作为对照组。
在 341 对双胞胎中，有 20.8%的人携带至少一个 D19H 等位基因，而无胆石症的对照组中为 9.4%。关联分析显示，D19H 阳性显著增加了胆石病的风险[比值比（OR），2.54；95%置信区间（CI），1.33-4.82；P = 0.004]。我们还发现胆石病与 Q604E 变异体之间存在正相关趋势（OR，1.47；95% CI，1.00-2.16；P = 0.052）。
携带杂合或纯合 ABCG8 D19H 基因型的双胞胎患胆石病的风险显著增加。我们的研究证实了 ABCG8 D19H 基因型是胆石病的主要危险因素。
