对一个大型欧洲队列中的炎症性肠病进行基因分析，支持与12号和16号染色体存在连锁关系。

Genetic analysis of inflammatory bowel disease in a large European cohort supports linkage to chromosomes 12 and 16.

作者信息

Curran M E, Lau K F, Hampe J, Schreiber S, Bridger S, Macpherson A J, Cardon L R, Sakul H, Harris T J, Stokkers P, Van Deventer S J, Mirza M, Raedler A, Kruis W, Meckler U, Theuer D, Herrmann T, Gionchetti P, Lee J, Mathew C, Lennard-Jones J

机构信息

AxyS Pharmaceuticals Inc., La Jolla, California, USA.

出版信息

Gastroenterology. 1998 Nov;115(5):1066-71. doi: 10.1016/s0016-5085(98)70075-7.

DOI:10.1016/s0016-5085(98)70075-7

PMID:9797359

Abstract

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a complex disorder of unknown etiology. Epidemiological investigations suggest a genetic basis for IBD. Recent genetic studies have identified several IBD linkages. The significance of these linkages will be determined by studies in large patient collections. The aim of this study was to replicate IBD linkages on chromosomes 12 and 16 in a large European cohort.

METHODS

Three hundred fifty-nine affected sibling pairs from 274 kindreds were genotyped using microsatellite markers spanning chromosomes 12 and 16. Affection status of the sibling pairs was defined as Crohn's disease (CD) or ulcerative colitis (UC).

RESULTS

Nonparametric statistical analyses showed linkage for both chromosomes. Two-point results for chromosome 12 peaked at D12S303 (logarithm of odds [LOD], 2.15; P = 0.003) for CD and at D12S75 (LOD, 0.92; P = 0.03) for UC. Multipoint analyses produced a peak LOD of 1.8 for CD. Chromosome 16 showed linkage for CD at marker D16S415 (LOD, 1.52; P = 0.007). Multipoint support peaked above markers D16S409 and D16S411 (LOD, 1.7).

CONCLUSIONS

These data are consistent with linkage of IBD to chromosomes 12 and 16. The replication of genetic risk loci in a large independent family collection indicates important and common susceptibility genes in these regions and will facilitate identification of genes involved in IBD.

摘要

背景与目的

炎症性肠病（IBD）是一种病因不明的复杂疾病。流行病学调查表明IBD存在遗传基础。近期的基因研究已确定了多个IBD连锁区域。这些连锁区域的意义将通过对大量患者群体的研究来确定。本研究的目的是在一个大型欧洲队列中复制12号和16号染色体上的IBD连锁区域。

方法

使用跨越12号和16号染色体的微卫星标记对来自274个家族的359对患病同胞进行基因分型。同胞对的患病状态定义为克罗恩病（CD）或溃疡性结肠炎（UC）。

结果

非参数统计分析显示两条染色体均存在连锁。12号染色体的两点分析结果显示，对于CD，在D12S303处达到峰值（优势对数[LOD]，2.15；P = 0.003），对于UC，在D12S75处达到峰值（LOD，0.92；P = 0.03）。多点分析得出CD的峰值LOD为1.8。16号染色体在标记D16S415处显示与CD存在连锁（LOD，1.52；P = 0.007）。多点支持在标记D16S409和D16S411上方达到峰值（LOD，1.7）。