title: Vitamin D receptor and megalin gene polymorphisms are associated with central adiposity status and changes among US adults.
abstract: 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 × 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 × 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 × 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.
authors.affiliation: National Institute on Aging , NIA/NIH/IRP, Baltimore, MD , USA.
authors.forename: May A
authors.initials: MA
authors.lastname: Beydoun
authors.affiliation: National Institute on Aging , NIA/NIH/IRP, Baltimore, MD , USA.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Graduate Program in Public Health, Eastern Virginia Medical School , Norfolk, VA , USA.
authors.forename: Hind A
authors.initials: HA
authors.lastname: Beydoun
authors.affiliation: Harvard School of Public Health , Department of Nutrtion, Boston, MA , USA.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Ding
authors.affiliation: National Institute on Aging , NIA/NIH/IRP, Baltimore, MD , USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: National Institute on Aging , NIA/NIH/IRP, Baltimore, MD , USA.
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
keywords: Adults; BLSA, Baltimore Longitudinal Study of Aging; Central adiposity; ECA, elevated central adiposity; LCA, latent class analysis; LD, linkage disequilibrium; Megalin; SICA, significant increase in central adiposity; SNP; SNPHAP, SNP halotype; SNPLC, SNP latent class; VDR, vitamin D receptor; Vitamin D receptor; WC, waist circumference; WHR, waist:hip ratio