Vitamin D receptor and megalin gene polymorphisms are associated with central adiposity status and changes among US adults

Beydoun, May A.; Tanaka, Toshiko; Beydoun, Hind A.; Ding, Eric L.; Ferrucci, Luigi; Zonderman, Alan B.

doi:10.1017/jns.2013.19

Cited by 17 publications

(19 citation statements)

References 39 publications

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“…Other elements in the vitamin D metabolism are the endocytic receptors megalin and cubulin, which are present in the renal tubuli cells [43] and enable transportation of the DBPvitamin D complexes and other filtered proteins into the cells [26]. Cubilin dysfunction may lead to urinary loss of vitamin D in the urine and cause abnormal metabolism of 25(OH)D [44], and MEGALIN polymorphisms are associated with adiposity [45]. Furthermore, an interaction between CUBILIN SNPs and serum 25(OH)D level was also described by Levin et al [25].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the vitamin D system and mortality - The Tromsø study

Jorde

Wilsgaard

Grimnes

2019

Preprint

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Background and objectiveVitamin D deficiency is associated with diabetes, cancer, immunological and cardiovascular diseases as well as increased mortality. It has, however, been difficult to show a causal relation in randomized, controlled trials. Mendelian randomization studies provide another option for testing causality, and results indicate relations between the serum 25hydroxyvitamin D (25(OH)D) level and some diseases, including mortality. We have from the Tromsø Study in 2012 published non-significant relations been vitamin D related single nucleotide polymorphisms (SNPs) and mortality, but have since then genotyped additional subjects, the observation time is longer and new SNPs have been included. Methods Genotyping was performed for SNPs in the NADSYN1, CYP2R1, VDR, CUBILIN and MEGALIN genes in 11 897 subjects who participated in the fourth survey of the Tromsø Study in 1994-1995. Serum 25(OH)D levels were measured in 6733 of these subjects. A genotype score based on SNPs in the NADSYN1 and CYP2R1 genes (related to the serum 25(OH)D level) and serum 25(OH)D percentile groups were created. Mortality data was updated till end of March 2017 and survival analysed with Cox regression adjusted for sex and age. ResultsDuring the observation period 5491 subjects died. The genotype score and the serum 25(OH)D percentile groups were (without Bonferroni correction) significantly related to mortality in favour of high serum 25(OH)D. None of the SNPs in the VDR or MEGALIN genes were related to mortality. However, for the rs12766939 in the CUBILIN gene with the major homozygote as reference, the hazard ratio for mortality for the minor homozygote genotype was 1.17 (1.06 -1.29), P < 0.002. This should be viewed with caution, as rs12766939 was not in Hardy-Weinberg equilibrium. ConclusionOur study confirms a probable causal but weak relation between serum 25(OH)D level and mortality. The relation between rs12766939 and mortality needs confirmation in more homogenous cohorts.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms in the vitamin D system and mortality - The Tromsø study

Jorde

Wilsgaard

Grimnes

2019

Preprint

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“…We entered dietary potential confounders that were linked to depression based on previous studies and included vitamins B-6, folate and B-12, total carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene), vitamin C and α-tocopherol 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 (all divided by total energy intake and expressed per 1000 kcal) and the ratio of n-3 polyunsaturated fatty acid (PUFA):n-6 PUFA. 55 Total energy intake was entered as a covariate to emulate a multivariate nutrient density model. 56 Models also included overall dietary quality as measured by the Healthy Eating Index (HEI-2010) total score, with details provided by the National Cancer Institute's Applied Research ( http://appliedresearch.cancer.gov/tools/hei/tools.html ) and the HANDLS ( http://handls.nih.gov/06Coll-dataDoc.htm ) websites.…”

Section: Methodsmentioning

confidence: 99%

White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults

Beydoun

et al. 2016

Transl Psychiatry

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Total white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex. In hypothesis 2, we examined reverse causality, by testing the relationship of depressive symptoms with change in TWBCC, PL and PN. Multiple linear mixed-effects regression models were performed to examine both the hypotheses. The sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (n=2009; n'=3501); Hypothesis 2 (n=2081; n'=3560). Among key findings (Hypothesis 1), in women, higher TWBCC was linked to a faster increase in depressive symptom total score (γ1112±s.e.: +0.81±0.28, P=0.003), with a slower increase over time in the positive affect subdomain coupled with faster increases in depressed affect and somatic complaints. Among women, baseline score on somatic complaints was positively associated with low PN (γ01a=+1.61±0.48, P<0.001) and high PL (γ01a=+1.16±0.45, P=0.011), whereas baseline score on positive affect was inversely related to higher PL (γ01a=−0.69±0.28, P=0.017). Results among men indicated that there was a positive cross-sectional relationship between low TWBCC and depressive symptoms, depressed affect and an inverse cross-sectional relationship with positive affect. However, over time, a low TWBCC in men was linked to a higher score on positive affect. There was no evidence of a bi-directional relationship between WBC parameters and depressive symptoms (Hypothesis 2). In sum, TWBCC and related markers were linked to depressive symptoms, mostly among women. Further longitudinal studies are needed to replicate this sex-specific association.

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“…The complex made of VDR and 1,25(OH) 2 D 3 modulates transcription of vitamin D responsive genes 12 and influences adipocyte differentiation 13 . The effect of VDR gene polymorphism can potentially be sex-specific as shown in at least one previous study with adiposity phenotypes 14 .…”

Section: Introductionmentioning

confidence: 93%

“…Epidemiological studies have confirmed associations of VDR polymorphisms with adiposity and other metabolic disturbances 6 , 14 – 23 . However, studies specifically examining adiposity outcomes either had small sample sizes (<400), (e.g 15 , 16 , 24 .)…”

Section: Introductionmentioning

confidence: 97%

Vitamin D Metabolism-Related Gene Haplotypes and Their Association with Metabolic Disturbances Among African-American Urban Adults

Beydoun

Hossain

Tajuddin

et al. 2018

Sci Rep

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Epidemiological studies have confirmed associations of the vitamin D receptor (VDR) and vitamin D-related gene polymorphisms with adiposity and other metabolic disturbances. Those associations may be sex-specific. We evaluated the cross-sectional and longitudinal relationships between metabolic disturbances and haplotypes constructed from single nucleotide polymorphisms of VDR (BsmI:G/A: rs1544410; ApaI:A/C: rs7975232; and TaqI:G/A: rs731236) and MEGALIN (rs3755166:G/A; rs2075252:C/T and rs2228171:C/T) genes, in a sample of African-American adults. From 1,024 African Americans participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS, 2004–2013, Baltimore, MD), our analyses included 539 participants with complete genetic, baseline covariate and metabolic outcome data (at baseline and follow-up). Mean ± SD period of follow-up was 4.64 ± 0.93 y. Multivariable-adjusted Cox proportional hazards and logistic regression models were conducted. Among key findings, in men, incident hypertension was inversely related to MEGALIN1 (GCC), [HR = 0.45, 95% CI: 0.23–0.90, p = 0.024]. Overall, there was a direct, linear dose-response association between VDR2 (AAG: BAt) and MetS at baseline [OR = 1.60, 95% CI: 1.11–2.31, p = 0.012], while among men, VDR3 (GAA: bAT) was inversely related to baseline MetS [OR = 0.40, 95% CI: 0.19–0.81, p = 0.011]. In conclusion, VDR and MEGALIN gene variations can affect prevalent MetS and the incidence rate of hypertension, respectively, among African-American urban adults.

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Vitamin D receptor and megalin gene polymorphisms are associated with central adiposity status and changes among US adults

Cited by 17 publications

References 39 publications

Polymorphisms in the vitamin D system and mortality - The Tromsø study

Polymorphisms in the vitamin D system and mortality - The Tromsø study

White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults

Vitamin D Metabolism-Related Gene Haplotypes and Their Association with Metabolic Disturbances Among African-American Urban Adults

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