RGD Reference Report - Replication of IGF2-INS-TH*5 haplotype effect on obesity in older men and study of related phenotypes. - Rat Genome Database

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Replication of IGF2-INS-TH*5 haplotype effect on obesity in older men and study of related phenotypes.

Authors: Rodriguez, S  Gaunt, TR  Dennison, E  Chen, XH  Syddall, HE  Phillips, DI  Cooper, C  Day, IN 
Citation: Rodriguez S, etal., Eur J Hum Genet. 2006 Jan;14(1):109-16.
RGD ID: 1601632
Pubmed: PMID:16251897   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.ejhg.5201505   (Journal Full-text)

Interindividual variation of the IGF2-INS-TH region influences risk of a variety of diseases and complex traits. Previous studies identified a haplotype (designated IGF2-INS-TH(*)5 and tagged by allele A of IGF2 ApaI, allele 9 of TH01 and class I alleles of INS VNTR) associated with low body mass index (BMI) in a cohort of UK men. We aimed here both to study whether previous findings relating (*)5 with weight are replicated in a different cohort of men (East Hertfordshire) characterised in more phenotypic detail and to test the effect of this haplotype on related subphenotypes. The PHASE program was used to identify (*)5 and not(*)5 haplotypes. A total of 490 haplotypes were derived from 131 men and 114 women, the frequency of (*)5 being around 9%. Specific tests of (*)5 haplotype (vs not(*)5 haplotypes) conducted included Student's t-test and multiple regression analyses. We observed replication of weight effect for the (*)5 haplotype in men: significant associations with lower BMI (-1.81 kg/m(2), P=0.009), lower waist circumference (-6.3 cm, P=0.001) and lower waist-hip ratio (-5%, P<0.001). This haplotype also marks nearly two-fold lower 120 min insulin (P=0.004) as well as low baseline insulin (-11.02 pmol/l, P=0.043) and low 30 min insulin (-64.44 pmol/l, P=0.072) in a glucose tolerance test. No association between (*)5 and these traits was found in women. Our results, taken together with other data on IGFII levels and TH activity, point to the importance of (*)5 as an integrated polygenic haplotype relevant to obesity and insulin response to glucose in men.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
THHumanobesity resistanceIAGP DNA:polymorphism:intron:g.1170_1173dupTCAT (human)RGD 
ThRatobesity resistanceISOTH (Homo sapiens)DNA:polymorphism:intron:g.1170_1173dupTCAT (human)RGD 
ThMouseobesity resistanceISOTH (Homo sapiens)DNA:polymorphism:intron:g.1170_1173dupTCAT (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Th  (tyrosine hydroxylase)

Genes (Mus musculus)
Th  (tyrosine hydroxylase)

Genes (Homo sapiens)
TH  (tyrosine hydroxylase)


Additional Information