The role of genetic susceptibility in the association of low birth weight with type 2 diabetes

被引:51
作者
Frayling, TM [1 ]
Hattersley, AT [1 ]
机构
[1] Univ Exeter, Sch Postgrad Med & Hlth Sci, Dept Diabet & Vasc Med, Exeter EX2 5AX, Devon, England
基金
美国国家卫生研究院;
关键词
D O I
10.1093/bmb/60.1.89
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We suggest that altered fetal growth and type 2 diabetes may be two phenotypes of the same genotype - in other words the 'thrifty phenotype' is the result of a 'thrifty genotype'. Supporting this there is strong evidence that paternal factors and, therefore, genes influence fetal growth and that these paternal genes affecting fetal growth may also alter diabetes risk. Further study is needed to determine whether common gene variants can explain the association between reduced birth weight and increased risk of type 2 diabetes. If the genetic hypothesis is true, common diabetes genes are likely to have subtle effects on insulin secretion and/or action and, therefore, subtle effects on fetal growth. Large cohorts of infants and their parents will be required probably in the region of thousands rather than hundreds - to identify gene variants that may explain the association between reduced birth weight and increased risk of type 2 diabetes. All previously described associations between birth weight and type 2 diabetes have required many hundreds of subjects and it is likely that the geneticists and the 'programmists' are trying to identify very subtle physiological effects.
引用
收藏
页码:89 / 101
页数:13
相关论文
共 58 条
[1]   β-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the β-cell phenotype and maturity onset diabetes [J].
Ahlgren, U ;
Jonsson, J ;
Jonsson, L ;
Simu, K ;
Edlund, H .
GENES & DEVELOPMENT, 1998, 12 (12) :1763-1768
[2]  
[Anonymous], 1977, The pregnant Diabetic and Her Newborn . Problems and Management
[3]   PRENATAL-DIAGNOSIS OF FAMILIAL NEONATAL HYPERINSULINEMIA [J].
APARICIO, L ;
CARPENTER, MW ;
SCHWARTZ, R ;
GRUPPUSO, PA .
ACTA PAEDIATRICA, 1993, 82 (08) :683-686
[4]  
BAKER J, 1993, CELL, V75, P73, DOI 10.1016/0092-8674(93)90680-O
[5]  
Barker D J, 1992, Paediatr Perinat Epidemiol, V6, P35, DOI 10.1111/j.1365-3016.1992.tb00741.x
[6]   FETAL AND PLACENTAL SIZE AND RISK OF HYPERTENSION IN ADULT LIFE [J].
BARKER, DJP ;
BULL, AR ;
OSMOND, C ;
SIMMONDS, SJ .
BRITISH MEDICAL JOURNAL, 1990, 301 (6746) :259-262
[7]  
Barkhouse KL, 1998, J ANIM SCI, V76, P2287
[8]   RELATION OF BIRTH-WEIGHT TO MATERNAL PLASMA-GLUCOSE AND INSULIN CONCENTRATIONS DURING NORMAL-PREGNANCY [J].
BRESCHI, MC ;
SEGHIERI, G ;
BARTOLOMEI, G ;
GIRONI, A ;
BALDI, S ;
FERRANNINI, E .
DIABETOLOGIA, 1993, 36 (12) :1315-1321
[9]   INSULIN SECRETORY ABNORMALITIES IN SUBJECTS WITH HYPERGLYCEMIA DUE TO GLUCOKINASE MUTATIONS [J].
BYRNE, MM ;
STURIS, J ;
CLEMENT, K ;
VIONNET, N ;
PUEYO, ME ;
STOFFEL, L ;
TAKEDA, J ;
PASSA, P ;
COHEN, D ;
BELL, GI ;
VELHO, G ;
FROGUEL, P ;
POLONSKY, KS .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (03) :1120-1130
[10]   Mitochondrial 16189 variant, thinness at birth, and type-2 diabetes [J].
Casteels, K ;
Ong, K ;
Phillips, D ;
Bendall, H ;
Pembrey, M ;
Poulton, J ;
Dunger, D .
LANCET, 1999, 353 (9163) :1499-1500