Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth |
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Authors: | Clive J Petry Pura Rayco-Solon Anthony J C Fulford John D H Stead Dianne L Wingate Ken K Ong Giorgio Sirugo Andrew M Prentice David B Dunger |
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Institution: | 1.Department of Paediatrics, Box 116, Addenbrooke’s Hospital,University of Cambridge,Cambridge,UK;2.MRC International Nutrition Group,London School of Hygiene and Tropical Medicine,London,UK;3.MRC Keneba, Medical Research Council Laboratories,Banjul,The Gambia;4.Unità di Genetica Medica, Ospendale San Pietro and Dipartimento di Biopatologia e Diagnostica per Immagini,,Università di Tor Vergata,Rome,Italy;5.Department of Genetics,University of Leicester,Leicester,UK;6.Institute of Neuroscience,Carleton University,Ottawa,Canada;7.MRC Epidemiology Unit,Cambridge,UK |
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Abstract: | 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. |
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