Localization of a susceptibility gene for type 2 diabetes to chromosome 5q34-q35.2

被引：131

作者：

Reynisdottir, I

Thorleifsson, G

Benediktsson, R

Sigurdsson, G

Emilsson, V

Einarsdottir, AS

Hjorleifsdottir, EE

Orlygsdottir, GT

Bjornsdottir, GT

Saemundsdottir, J

Halldorsson, S

Hrafnkelsdottir, S

Sigurjonsdottir, SB

Steinsdottir, S

Martin, M

Kochan, JP

Rhees, BK

Grant, SFA

Frigge, ML

Kong, A

Gudnason, V

Stefansson, K

Gulcher, JR

机构：

[1] deCODE Genet, Reykjavik, Iceland

[2] Iceland Heart Assoc, Reykjavik, Iceland

[3] Landspitali Univ Hosp, Reykjavik, Iceland

[4] Hoffmann La Roche Inc, Nutley, NJ 07110 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2003年 / 73卷 / 02期

关键词：

D O I：

10.1086/377139

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report a genomewide linkage study of type 2 diabetes ( T2D [MIM 125853]) in the Icelandic population. A list of type 2 diabetics was cross-matched with a computerized genealogical database clustering 763 type 2 diabetics into 227 families. The diabetic patients and their relatives were genotyped with 906 microsatellite markers. A nonparametric multipoint linkage analysis yielded linkage to 5q34-q35.2 (LOD = 2.90, P = 1.29 x 10(-4)) in all diabetics. Since obesity, here defined as body mass index (BMI) greater than or equal to 30 kg/m(2), is a key risk factor for the development of T2D, we studied the data either independently of BMI or by stratifying the patient group as obese ( BMI greater than or equal to 30) or nonobese (BMI < 30). A nonparametric multipoint linkage analysis yielded linkage to 5q34 - q35.2 (LOD = 3.64, P = 2.12 x 10(-5)) in the nonobese diabetics. No linkage was observed in this region for the obese diabetics. Linkage analysis conditioning on maternal transmission to the nonobese diabetics resulted in a LOD score of 3.48 (P = 3.12 x 10(-5)) in the same region, whereas conditioning on paternal transmission led to a substantial drop in the LOD score. Finally, we observed potential interactions between the 5q locus and two T2D susceptibility loci, previously mapped in other populations.

引用

页码：323 / 335

页数：13

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