Absence of Birth-Weight Lowering Effect of ADCY5 and Near CCNL, but Association of Impaired Glucose-Insulin Homeostasis with ADCY5 in Asian Indians

Senthil K Vasan, Matt J Neville, Belavendra Antonisamy, Prasanna Samuel, Caroline H Fall, Finney S Geethanjali, Nihal Thomas, Palany Raghupathy, Kerstin Brismar and Fredrik Karpe

PLOS ONE, 2011, vol. 6, issue 6, 1-6

Abstract: Background: A feature of the Asian Indian phenotype is low birth weight with increased adult type 2 diabetes risk. Most populations show consistent associations between low birth weight and adult type 2 diabetes. Recently, two birth weight-lowering loci on chromosome 3 (near CCNL1 and ADCY5) were identified in a genome-wide association study, the latter of which is also a type 2 diabetes locus. We therefore tested the impact of these genetic variants on birth weight and adult glucose/insulin homeostasis in a large Indian birth cohort. Methodology/Principal Findings: Adults (n = 2,151) enrolled in a birth cohort (established 1969-73) were genotyped for rs900400 (near CCNL1) and rs9883204 (ADCY5). Associations were tested for birth weight, anthropometry from infancy to adulthood, and type 2 diabetes related glycemic traits. The average birth weight in this population was 2.79±0.47 kg and was not associated with genetic variation in CCNL1 (p = 0.87) or ADCY5 (p = 0.54). Allele frequencies for the ‘birth weight-lowering’ variants were similar compared with Western populations. There were no significant associations with growth or adult weight. However, the ‘birth weight-lowering’ variant of ADCY5 was associated with modest increase in fasting glucose (β 0.041, p = 0.027), 2-hours glucose (β 0.127, p = 0.019), and reduced insulinogenic index (β -0.106, p = 0.050) and 2-hour insulin (β -0.058, p = 0.010). Conclusions: The low birth weight in Asian Indians is not even partly explained by genetic variants near CCNL1 and ADCY5 which implies that non-genetic factors may predominate. However, the ‘birth-weight-lowering’ variant of ADCY5 was associated with elevated glucose and decreased insulin response in early adulthood which argues for a common genetic cause of low birth weight and risk of type 2 diabetes.

Date: 2011
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0021331

DOI: 10.1371/journal.pone.0021331

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