Association of the RS9883204 polymorphism in ADCY5 with birth weight and risk of gestational diabetes mellitus in the Maltese population

Abstract

Birth weight is a complex multifactorial trait and an important indicator of an infant`s future health. Birth weight is influenced by various placental, environmental, maternal as well as genetic factors. Low birth weight due to restricted foetal growth is associated with high rates of perinatal morbidity and mortality, neonatal complications and a higher incidence of later-life chronic diseases such as type 2 diabetes, hypertension, and cardiovascular disease. A meta-analysis of genome-wide association studies (GWAS) has identified an association between low birth weight and a single nucleotide polymorphism (SNP), rs9883204, located at 3q21 within the adenylate cyclase 5 (ADCY5) gene. No previous studies have investigated the genetic determinants of birth weight in the Maltese population. Using polymerase chain reaction (PCR) and Sanger sequencing, the association of rs9883204 in ADCY5 with birth weight and gestational diabetes mellitus (GDM) risk was investigated, in paired maternal and neonatal cohorts. The major allele frequency (C) in the maternal cohort was 80% and the minor allele frequency (T) was 20%. The major allele frequency (C) in the neonatal cohort was 77% and the minor allele frequency (T) was 23%. The polymorphism at rs9883204 (ADCY5) showed no correlation with birth weight or GDM risk in the Maltese population. Both birth weight and GDM have a heterogeneous nature and this is a possible explanation for the observed lack of association, as a single polymorphism is unlikely to explain these complex outcomes in a small sample of the Maltese population.