Genetic risk factors for obesity (MAF MC4R and FTO-polymorphisms) in a large cohort of German VLBW infants

Aims: Variants in MAF, MC4R and FTO have repeatedly been associated with obesity and partly with Type II diabetes. Small for gestational age infants have an increased risk to become obese and to develop a metabolic syndrome. We hypothesised that these variants could be associated with lower birth weight and with neonatal catch-up-growth thereby causing the association with obesity and Type II diabetes in adults. We tested these variants for association with preterm birth as well as birth weight and weight gain in German very low birth weight (VLBW) infants. Methods: We conducted a prospective multicenter cohort study to investigate the influence of genetic variants involved in gestational age, premature birth and outcomes of VLBW infants in 15 NICUs in Germany from September 2003 until January 2008. DNA samples were extracted from buccal swabs according to standard protocols. The SNP variants rs17782313 MC4R T=>C, rs1424233 MAF T=>C and rs9939609 FTO T=>A were genotyped using an allelic discrimination assay. Results: Genomic DNA of 2043 VLBW infants and 308 term born controls was available for genotyping. The polymorphisms were in Hardy Weinberg Equilibrium. 468 vlbw infants (23%) were small for gestational age (<10. percentile). The polymorphisms were not associated with birth weight below the 10. percentile, preterm-birth, or postnatal weight gain. Discussion: In this large cohort of German VLBW infants polymorphisms in MAF, MC4R and FTO were not associated with birth weight, preterm-birth, and weight gain. We did not find a genetic cause for the higher incidence of metabolic syndrome in small for gestational age infants. Since we were also not able to find an association of these polymorphisms with weight gain in neonates, it may be hypothesized, that this polymorphism only affects food intake behaviour and hunger, rather than metabolism and energy consumption. The role of gene-environment interactions might overshadow the actual effect of the polymorphisms in our population even though it was conducted in the very controlled environment of intensive care units.