Genome-wide search for type 2 diabetes in Japanese affected sib-pails confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p

被引：195

作者：

Mori, Y

Otabe, S

Dina, C

Yasuda, K

Populaire, C

Lecoeur, C

Vatin, V

Durand, E

Hara, K

Okada, T

Tobe, K

Boutin, P

Kadowaki, T

Froguel, P

机构：

[1] Inst Pasteur, CNRS 8090, Inst Biol, F-59019 Lille, France

[2] Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo, Japan

[3] Queen Mary Univ London, Barts & London Genome Ctr, London E1 4NS, England

来源：

DIABETES | 2002年 / 51卷 / 04期

基金：

英国医学研究理事会;

关键词：

D O I：

10.2337/diabetes.51.4.1247

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The genetic background that predisposes the Japanese population to type 2 diabetes is largely unknown. Therefore, we conducted a 10-cM genome-wide scan for type 2 diabetes traits in the 359 affected individuals from 159 families, yielding 224 affected sib-pairs of Japanese origin. Nonparametric multipoint linkage analyses performed in the whole population showed one suggestive linked region on 11p13-p12 (maximum logarithm of odds score [MLS] 3.08, near Pax6) and seven potentially linked regions (MLS >1.17) at 1p36-p32, 2q34, 3q26-q28, 6p23, 7p22-p21, 15q13-q21, and 20q12-q13 (near the gene for hepatocyte nuclear factor-4alpha [HNF-4alpha]). Subset analyses according to maximal BMI and early age at diagnosis added suggestive evidence of linkage with type 2 diabetes at 7p22-p21 (MLS 3.51), 15q13-q21 (MLS 3.91), and 20q12-q13 (MLS 2.32). These results support previous indication for linkage found on chromosome 3q, 15q, and 20q in other populations and identifies two new potential loci on 7p and 11p that may confer genetic risk for type 2 diabetes in the Japanese population.

引用

页码：1247 / 1255

页数：9

共 46 条

[1] Loci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans [J].

Cox, NJ ;

Frigge, M ;

Nicolae, DL ;

Concannon, P ;

Hanis, CL ;

Bell, GI ;

Kong, A .

NATURE GENETICS, 1999, 21 (02) :213-215

[2] Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans [J].

Duggirala, R ;

Blangero, J ;

Almasy, L ;

Dyer, TD ;

Williams, KL ;

Leach, RJ ;

O'Connell, P ;

Stern, MP .

AMERICAN JOURNAL OF HUMAN GENETICS, 1999, 64 (04) :1127-1140

[3] A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians [J].

Elbein, SC ;

Hoffman, MD ;

Teng, K ;

Leppert, MF ;

Hasstedt, SJ .

DIABETES, 1999, 48 (05) :1175-1182

[4] SEQUENCE VARIATIONS OF THE GLUCOKINASE GENE IN JAPANESE SUBJECTS WITH NIDDM [J].

ETO, K ;

SAKURA, H ;

SHIMOKAWA, K ;

KADOWAKI, H ;

HAGURA, R ;

AKANUMA, Y ;

YAZAKI, Y ;

KADOWAKI, T .

DIABETES, 1993, 42 (08) :1133-1137

[5] PREVALENCE OF DIABETES-MELLITUS AND IMPAIRED GLUCOSE-TOLERANCE AMONG 2ND-GENERATION JAPANESE-AMERICAN MEN [J].

FUJIMOTO, WY ;

LEONETTI, DL ;

KINYOUN, JL ;

NEWELLMORRIS, L ;

SHUMAN, WP ;

STOLOV, WC ;

WAHL, PW .

DIABETES, 1987, 36 (06) :721-729

[6] Organization and partial sequence of the hepatocyte nuclear factor-4 alpha MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY [J].

Furuta, H ;

Iwasaki, N ;

Oda, N ;

Hinokio, Y ;

Horikawa, Y ;

Yamagata, K ;

Yano, N ;

Sugahiro, J ;

Ogata, M ;

Ohgawara, H ;

Omori, Y ;

Iwamoto, Y ;

Bell, GI .

DIABETES, 1997, 46 (10) :1652-1657

[7] The Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study.: I.: An autosomal genome scan for genes that predispose to type 2 diabetes [J].

Ghosh, S ;

Watanabe, RM ;

Valle, TT ;

Hauser, ER ;

Magnuson, VL ;

Langefeld, CD ;

Ally, DS ;

Mohlke, KL ;

Silander, K ;

Kohtamäki, K ;

Chines, P ;

Balow, J ;

Birznieks, G ;

Chang, J ;

Eldridge, W ;

Erdos, MR ;

Karanjawala, ZE ;

Knapp, JI ;

Kudelko, K ;

Martin, C ;

Morales-Mena, A ;

Musick, A ;

Musick, T ;

Pfahl, C ;

Porter, R ;

Rayman, JB ;

Rha, D ;

Segal, L ;

Shapiro, S ;

Sharaf, R ;

Shurtleff, B ;

So, A ;

Tannenbaum, J ;

Te, C ;

Tovar, J ;

Unni, A ;

Welch, C ;

Whiten, R ;

Witt, A ;

Blaschak-Harvan, J ;

Douglas, JA ;

Duren, WL ;

Epstein, MP ;

Fingerlin, TE ;

Kaleta, HS ;

Lange, EM ;

Li, C ;

McEachin, RC ;

Stringham, HM ;

Trager, E .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (05) :1174-1185

[8] Type 2 diabetes: Evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs [J].

Ghosh, S ;

Watanabe, RM ;

Hauser, ER ;

Valle, T ;

Magnuson, VL ;

Erdos, MR ;

Langefeld, CD ;

Balow, J ;

Ally, DS ;

Kohtamaki, K ;

Chines, P ;

Birznieks, G ;

Kaleta, HS ;

Musick, A ;

Te, C ;

Tannenbaum, J ;

Eldridge, W ;

Shapiro, S ;

Martin, C ;

Witt, A ;

So, A ;

Chang, J ;

Shurtleff, B ;

Porter, R ;

Kudelko, K ;

Unni, A ;

Segal, L ;

Sharaf, R ;

Blaschak-Harvan, J ;

Eriksson, J ;

Tenkula, T ;

Vidgren, G ;

Ehnholm, C ;

Tuomilehto-Wolf, E ;

Hagopian, W ;

Buchanan, TA ;

Tuomilehto, J ;

Bergman, RN ;

Collins, FS ;

Boehnke, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (05) :2198-2203

[9] Relationship estimation in affected rib pair analysis of late-onset diseases [J].

Goring, HHH ;

Ott, J .

EUROPEAN JOURNAL OF HUMAN GENETICS, 1997, 5 (02) :69-77

[10] FAMILY HISTORY OF DIABETIC-PATIENTS IN JAPAN [J].

HAGURA, R ;

MATSUDA, A ;

KUZUYA, T ;

YOSHINAGA, H ;

KOSAKA, K .

DIABETES RESEARCH AND CLINICAL PRACTICE, 1994, 24 :S69-S73

← 1 2 3 4 5 →