Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians.

ABSTRACT: 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.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 (? 0.041, p?=?0.027), 2-hours glucose (? 0.127, p?=?0.019), and reduced insulinogenic index (? -0.106, p?=?0.050) and 2-hour insulin (? -0.058, p?=?0.010).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.

SUBMITTER: Vasan SK 

PROVIDER: S-EPMC3119677 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature