Premature termination codon rs67047829 in ERV3-1 may be protective against obesity

Abstract Premature termination codons are usually single nucleotide polymorphisms which can have high, but ethnically-dependent, prevalence in a population. The aim of this fishing study was to assess all such premature termination codons (n=140) from a database (with 551915 exonic variants; HumanCoreExome-24 v1.0 and v1.1 BeadChip) with association with obesity in a large sample (n=5757) of the Polish population. Statistical analyses were conducted using regression models with body mass index (BMI) as a continuous variable. Interactions with year of birth and sex; and recessive, dominant and heterozygote models for males and females together and then separately were assessed. A significant association, which was interaction independent, was found between the ERV3-1: rs67047829 heterozygote model and BMI with both sexes together (p-value adjusted for year of birth and sex: 0.001; BMI for AA, GA, GG: means (standard deviations): 22.9 (3.68), 24.7 (4.44), 24.9 (4.59)). Corresponding values for males, but not for females, were also significant: (p=0.003; AA 22.2 (3.96), GA 23.8 (4.44), GG 24.3 (4.96)). As rs67047829 produces a stop codon in the Endogenous retrovirus group 3 member 1, envelope protein, the mRNA of which is highly expressed in adipose tissue, it is possible this premature termination codon provides protective effect against obesity.