Samudrala Narahari, Farook Vidya S, Dodd Gerald D, Puppala Sobha, Schneider Jennifer, Fowler Sharon, Granato Richard, Dyer Thomas D, Arya Rector, Almasy Laura, Jenkinson Christopher P, Diehl Andrew K, Blangero John, Duggirala Ravindranath
Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, TX 78245-0549, USA.
Hum Biol. 2008 Feb;80(1):11-28. doi: 10.3378/1534-6617(2008)80[11:AGLATI]2.0.CO;2.
The significance of gallbladder wall thickness (GBWT) in regard to gallbladder disease (GBD) is not completely understood. Thickening of the gallbladder wall has been observed in patients with acute calculous and acalculous cholecystitis and chronic cholecystitis. However, various pathologic processes, such as gallbladder cancer and nonbiliary disorders such as liver cirrhosis and viral hepatitis, could also cause thickening of the gallbladder wall. To date, there is no report available on the genetic factors influencing GBWT. Therefore we sought to estimate the heritability (h2) of GBWT and to perform a genome-wide search to identify the susceptibility genes for GBWT, using data from the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), a family study of Mexican Americans. GBWT was measured by ultrasound. After adjusting for the significant effects of age, sex, GBD (i.e., asymptomatic gallstones), metabolic syndrome, and duration of type 2 diabetes (T2DM), GBWT was found to be under significant and appreciable additive genetic influences (h2 +/- SE = 0.38 +/- 0.09, P < 0.0001). The strongest evidence for linkage occurred between markers D11S912 and D11S968 on chromosome 11q24-q25 (LOD = 2.7), where we have already shown suggestive evidence for linkage of GBD (LOD = 2.7) in a subset of our SAFDGS data. Potential evidence for linkage occurred at markers D1S1728 (1p31.1; LOD = 1.4) and D16S748 (16p13.1; LOD = 1.4), respectively. In conclusion, our study provides suggestive evidence for linkage of GBWT on chromosome 11q in Mexican Americans, and future tasks of mapping susceptibility gene(s) for GBD and its related traits, such as GBWT, in this chromosomal region can be fruitful.
胆囊壁厚度（GBWT）在胆囊疾病（GBD）方面的意义尚未完全明确。在急性结石性和非结石性胆囊炎以及慢性胆囊炎患者中观察到胆囊壁增厚。然而，各种病理过程，如胆囊癌以及非胆道疾病，如肝硬化和病毒性肝炎，也可能导致胆囊壁增厚。迄今为止，尚无关于影响GBWT的遗传因素的报道。因此，我们试图利用来自圣安东尼奥家族糖尿病/胆囊研究（SAFDGS）（一项针对墨西哥裔美国人的家族研究）的数据，估算GBWT的遗传力（h2）并进行全基因组搜索，以确定GBWT的易感基因。GBWT通过超声测量。在调整年龄、性别、GBD（即无症状胆结石）、代谢综合征和2型糖尿病（T2DM）病程的显著影响后，发现GBWT受到显著且可观的加性遗传影响（h2 +/- SE = 0.38 +/- 0.09，P < 0.0001）。最强的连锁证据出现在11号染色体q24 - q25上的标记D11S912和D11S968之间（LOD = 2.7），在我们SAFDGS数据的一个子集中，我们已经显示出GBD连锁的提示性证据（LOD = 2.7）。潜在的连锁证据分别出现在标记D1S1728（1p31.1；LOD = 1.4）和D16S748（16p13.1；LOD = 1.4）处。总之，我们的研究为墨西哥裔美国人中GBWT在11号染色体q上的连锁提供了提示性证据，并且在该染色体区域绘制GBD及其相关性状（如GBWT）的易感基因的未来任务可能会取得丰硕成果。
