Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.
The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits.
Department of Paediatrics, Box 116, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge, CB2 0QQ, UK. cjp1002@cam.ac.uk
Clive J
CJ
Petry
Pura
P
Rayco-Solon
Anthony J C
AJ
Fulford
John D H
JD
Stead
Dianne L
DL
Wingate
Ken K
KK
Ong
Giorgio
G
Sirugo
Andrew M
AM
Prentice
David B
DB
Dunger
D000483:Alleles; D053198:Child Nutrition Sciences; D017931:DNA Primers / Q000235:genetics; D005220:Fathers; D005260:Female; D005714:Gambia; D014644:Genetic Variation; D005838:Genotype; D006128:Growth / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics*; D008297:Male; D009035:Mothers; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D017931:DNA Primers; D007328:Insulin