rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population

Abstract

There is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m²: [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10^-5; beta: - 0.0458, 95% confidence interval (CI) - 0.0732 : - 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10^-4; beta: - 0.0573, CI - 0.0947 : - 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in ERV3-1 which shares an exonic region and possibly promoter with ZNF117, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting ERV3-1/ZNF117 might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression.