Examining the candidacy of ghrelin as a gene responsible for variation in adult stature in a United Kingdom population with type 2 diabetes.
BACKGROUND
Recently, a quantitative trait locus for stature was reported on chromosome 3p26 in patients with type 2 diabetes.


OBJECTIVE
Given that ghrelin is a peptide involved in GH release and located on 3p26, we hypothesized that variation within its gene (GHRL) may be responsible for the quantitative trait locus on 3p26.


METHODS
The evidence for linkage around GHRL was refined with the genotyping of an additional four microsatellites (D3S4545, D3S1537, D3S1597, and D3S3611), giving a total of 27 markers, followed by multipoint variance components linkage analysis. Probands from the linkage families were typed for five common single nucleotide polymorphisms (SNPs) within GHRL and tested for association with adult stature using haplotype trend regression.


RESULTS
The maximum multipoint evidence for linkage between adult stature and the 27 microsatellites yielded an LOD score of 2.58 (P = 0.0003) between D3S1297 and D3S1304. Five common (frequency of > or =5%) SNPs were typed in the probands [two promoter SNPs (rs27647 and rs26802), two exonic (rs696217 and rs4684677), and one intronic (rs35683)] capturing 80% of the total common variation in GHRL. No association was found between any SNP (or haplotypes thereof) and adult stature.


CONCLUSIONS
Common genetic variation within GHRL is not responsible for variation in adult stature in this population.
Gueorguiev
Maria
M
Reader in Endocrine Research, Department of Endocrinology, Room 114C, John Vane Science Centre, Barts and the London Medical School, Charterhouse Square, London, UK.
Wiltshire
Steven
S
Garcia
Edwin A
EA
Mein
Charles
C
Lecoeur
Cecile
C
Kristen
Brigitte
B
Allotey
Rebecca
R
Hattersley
Andrew T
AT
Walker
Mark
M
O'rahilly
Stephen
S
Froguel
Philippe
P
Grossman
Ashley B
AB
McCarthy
Mark I
MI
Hitman
Graham A
GA
Korbonits
Márta
M
D000328:Adult; D000368:Aged; D001827:Body Height / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D054439:Ghrelin; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D036361:Peptide Hormones / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
D054439:Ghrelin; D036361:Peptide Hormones