Vitamin D-related Genes and Metabolic Disorders
Ключови думи
Резюме
Описание
Adiposity, especially central adiposity, is a key component of the metabolic syndrome (MetS), which is accompanied by hyperglycemia, elevated blood pressure, lower HDL cholesterol and hypertriglyceridemia.(Ford, et al., 2003,Grundy, 1999)_ENREF_4 MetS increases the risk of type 2 diabetes (T2D) and cardiovascular disease by 1.7- and 5-folds, respectively.(Alberti, et al., 2009,Ford, et al., 2003,Galassi, et al., 2006) MetS is heritable and polygenic.(Maes, et al., 1997) Genetic variability contributes to 16%-85% of changes in Body Mass Index (BMI)(Yang, et al., 2007) and 37%-81% in waist circumference (WC) (e.g.(Ochs-Balcom, et al., 2011)). MetS is a major public health concern, increasing all-cause mortality rates, disability and health care costs.(Appels and Vandenbroucke, 2006,Bender, et al., 2006,Colditz, 1999,Doig, 2004,Ferrucci and Alley, 2007,Hill, et al., 2004,Solomon and Manson, 1997,Stevens, 2000,Wolf and Colditz, 1998) Obesity is implicated in the etiology of vitamin D deficiency. Serum 25-hydroxyvitamin D [25(OH)D] concentration correlates inversely with adiposity.(Beydoun, et al., 2010,Dorjgochoo, et al., 2012) Conversely, vitamin D3 may play a role in obesity by modulating intracellular calcium homeostasis, because higher intracellular calcium triggers lipogenesis and suppresses lipolysis.(Zemel, 2003) Many organs express vitamin D receptor (VDR), a part of the nuclear hormone receptor super-family. The VDR-1,25(OH)2D3 complex modulates transcription of vitamin D responsive genes(Kato, 2000) and influences adipocyte differentiation both in vitro and in vivo.(Wood, 2008) Epidemiological studies have shown associations of VDR gene polymorphisms with adiposity and related metabolic disorders.(Filus, et al., 2008,Grundberg, et al., 2004,Gu, et al., 2009,Ochs-Balcom, et al., 2011,Oh and Barrett-Connor, 2002,Ortlepp, et al., 2001,Ortlepp, et al., 2003,Speer, et al., 2001,Ye, et al., 2001) However, studies specifically examining adiposity outcomes either had small sample sizes (<400), (e.g.(Filus, et al., 2008,Grundberg, et al., 2004,Speer, et al., 2001)) or were restricted to one sex, (e.g. (Grundberg, et al., 2004,Ochs-Balcom, et al., 2011)) but more importantly were all cross-sectional or case-control by design.(Filus, et al., 2008,Grundberg, et al., 2004,Gu, et al., 2009,Ochs-Balcom, et al., 2011,Oh and Barrett-Connor, 2002,Ortlepp, et al., 2001,Ortlepp, et al., 2003,Speer, et al., 2001,Ye, et al., 2001) MEGALIN (aka low-density lipoprotein receptor-related protein-2 [LRP-2]), is the endocytic vitamin D-binding protein receptor which allows vitamin D entry into cells and whose expression is directly regulated by both vitamin D (Gressner, et al., 2008)) and vitamin A.(Liu, et al., 1998) MEGALIN may influences obesity by mediating leptin transport through the blood-brain barrier and modulating leptin signaling,(Dietrich, et al., 2008) or by facilitating transcytosis of its precursor hormone thyroglobulin.(Lisi, et al., 2005) Collectively, leptin and thyroid hormones affect adiposity through energy metabolism regulation.(Beydoun, et al., 2011) MEGALIN acting also as the receptor for sex-hormone binding globulin (SHBG) may play a role in the interaction between estrogen, vitamin D and intracellular calcium in adipocytes, resulting in sex-specific effects of MEGALIN polymorphisms on obesity phenotypes.(Ding, et al., 2008) In this study, it is hypothesized that selected polymorphisms in VDR and MEGALIN genes have sex-specific associations with several key metabolic disturbances in a longitudinal study of African-American urban adults.
Дати
Последна проверка: | 08/31/2017 |
Първо изпратено: | 09/07/2017 |
Очаквано записване подадено: | 09/10/2017 |
Първо публикувано: | 09/11/2017 |
Изпратена последна актуализация: | 09/10/2017 |
Последна актуализация публикувана: | 09/11/2017 |
Действителна начална дата на проучването: | 08/17/2004 |
Приблизителна дата на първично завършване: | 07/06/2013 |
Очаквана дата на завършване на проучването: | 07/06/2013 |
Състояние или заболяване
Фаза
Критерии за допустимост
Възрасти, отговарящи на условията за проучване | 30 Years Да се 30 Years |
Полове, допустими за проучване | All |
Метод за вземане на проби | Probability Sample |
Приема здрави доброволци | Да |
Критерии | Inclusion Criteria: 1. 3,720 baseline participants (mean±SD age(y) of 48.3±9.4, 45.3% men, and 59.1% African-American), 2. Genetic data were available on 1,024 African-American participants. 3. Incomplete covariate data reduced the sample to n=769, while additional exclusions lead to a sample size ranging between 574 and 598 participants, with 539 having complete data on all baseline and follow-up outcome measures (cross-sectional part of the analysis). 4. In the longitudinal analysis, metabolic disturbance-free at baseline participants were selected for each outcome. Sample sizes ranged from n=246 (central obesity-free) to n=466 (hyperglycemia-free). 5. There were n=294 MetS-free individuals at baseline. Exclusion Criteria: 1. Whites in HANDLS, since they did not have any genetic data collected. 2. All African-Americans in HANDLS without genetic data collected. 3. All African-Americans in HANDLS with genetic data collected, who had incomplete data on key outcome variables and/or basic covariates of interest. |
Резултат
Първични изходни мерки
1. Obesity [2004-2013]
2. Central Obesity [2004-2013]
3. Metabolic Syndrome [2004-2013]