DIETARY SURVEYS AND NUTRITIONAL EPIDEMIOLOGY Vitamin D receptor and megalin gene polymorphisms are associated with central adiposity status and changes among US adults

We examined longitudinal associations of vitamin D receptor (VDR) and megalin (LRP2; LDL receptor-related protein-2) gene polymorphisms with central adiposity. We used data from the Baltimore Longitudinal Study of Aging (BLSA), an ongoing prospective open cohort study. Study participants consisted of non-Hispanic white adults residing in Baltimore city, with one or more visits at age >= 50 years, and complete data (n 609-617). Repeated assessments on waist circumference (WC) and waist: hip ratio (WHR) were available. Multiple linear mixed models were used to estimate mid-follow-up age central adiposity level and annual rate of change with cut-points set at the sex-specific 80th percentile. The four binary outcomes were: 'elevated central adiposity' (ECA-WC and ECA-WHR) and 'significant increase in central adiposity' (SICA-WC and SICA-WHR). SNP for VDR (four SNP: (1) rs11568820 (CdX-2: T/C); (2) rs1544410 (BsmI: G/A); (3) rs7975232 (ApaI: A/C); (4) rs731236 (TaqI: G/A)) and Megalin (three SNP: (1) rs3755166: G/A; (2) rs2075252: C/T; (3) rs4668123: C/T) genes were selected. SNP latent classes (SNPLC) and SNP haplotypes (SNPHAP) were created. Multiple logistic regression analyses indicated that, in men, higher ECA-WHR odds were associated with SNPLC Megalin2: rs3755166[-]/rs2075252[ TT]/rs4668123[ T-] (v. Megalin1: rs3755166[-]/rs2075252[ CC]/rs4668123[-]) (OR 2 . 87; 95 % CI 1 . 15, 7 . 12; P = 0 . 023) and that SNPLC Megalin3: rs3755166[-]/rs2075252[ CT]/ rs4668123[-] (v. Megalin1) was linked to lower SICA-WC odds (OR 0 . 48; 95 % CI 0 . 26, 0 . 88; P = 0 . 019) (P > 0 . 05 for sex x SNPLC). In women, VDR3 SNPHAP (GAA: bAT) was related to lower odds of ECA-WC (OR 0 . 37; 95 % CI 0 . 16, 0 . 87; P = 0 . 023) (P < 0 . 05 for sex x SNPHAP), VDR1 SNPHAP (GCA: baT) was associated with greater odds and VDR3 SNPHAP (GAA: bAT) with lower odds of SICA-WC (P > 0 . 05 for sex x SNPHAP). Vitamin D-related gene polymorphisms were associated with central adiposity status and change. Future mechanistic studies are needed to confirm those polymorphisms' biological significance to central adiposity.