Endocrinology and Metabolism

Review Article

Calcium & Bone Metabolism
Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer: Siva Swapna Kasarla, Vannuruswamy Garikapati, Yashwant Kumar, Sujatha Dodoala; Endocrinol Metab. 2022;37(3):392-407. Published online June 3, 2022; DOI: https://doi.org/10.3803/EnM.2021.1349

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Vitamin D has received considerable optimistic attention as a potentially important factor in many pathological states over the past few decades. However, the proportion of the active form of vitamin D metabolites responsible for biological activity is highly questionable in disease states due to flexible alterations in the enzymes responsible for their metabolism. For instance, CYP3A4 plays a crucial role in the biotransformation of vitamin D and other drug substances. Food-drug and/or drug-drug interactions, the disease state, genetic polymorphism, age, sex, diet, and environmental factors all influence CYP3A4 activity. Genetic polymorphisms in CYP450-encoding genes have received considerable attention in the past few decades due to their extensive impact on the pharmacokinetic and dynamic properties of drugs and endogenous substances. In this review, we focused on CYP3A4 polymorphisms and their interplay with vitamin D metabolism and summarized the role of vitamin D in calcium homeostasis, bone diseases, diabetes, cancer, other diseases, and drug substances. We also reviewed clinical observations pertaining to CYP3A4 polymorphisms among the aforementioned disease conditions. In addition, we highlighted the future perspectives of studying the pharmacogenetics of CYP3A4, which may have potential clinical significance for developing novel diagnostic genetic markers that will ascertain disease risk and progression.

Citations

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Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis
Mohamed I. Elsalahaty, Samar Sami Alkafaas, Aya O. Bashir, Khaled A. El-Tarabily, Mohamed T. El-Saadony, Eman H. Yousef
Frontiers in Genetics.2024;[Epub] CrossRef
Vitamin D in Melanoma: Potential Role of Cytochrome P450 Enzymes
Mohamed Ben-Eltriki, Erysa J. Gayle, Jhoanne M. Paras, Louisa Nyame-Addo, Manik Chhabra, Subrata Deb
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Heat stress as a potential risk factor for vitamin D deficiency
Martina Balducci, Letizia Pruccoli, Andrea Tarozzi
Medical Hypotheses.2023; 176: 111085. CrossRef
Association and Haplotype Analysis of the PON1, ITGB3 and CYP3A4 Genes, Strong Candidates for Familial Coronary Artery Disease Susceptibility
Faruk SAYDAM, İrfan DEĞİRMENCİ, Alparslan BİRDANE, Cansu ÖZBAYER, Taner ULUS, Mahmut ÖZDEMİR, Necmi ATA, Hasan Veysi GÜNEŞ
Online Türk Sağlık Bilimleri Dergisi.2023; 8(1): 81. CrossRef
Association of flame retardants, polybrominated diethyl ethers (PBDEs), with vitamin D in female subjects
Alexandra E. Butler, Edwina Brennan, Daniel S. Drage, Thozhukat Sathyapalan, Stephen L. Atkin
Chemosphere.2023; 338: 139488. CrossRef
Genetic variations of CYP3A4 on the metabolism of itraconazole in vitro
Sai-li Xie, Xiayan Zhu, Nanyong Gao, Qianmeng Lin, Chaojie Chen, Yun-jun Yang, Jian-ping Cai, Guo-xin Hu, Ren-ai Xu
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Original Articles

Seasonal Variation in Serum 25-Hydroxyvitamin D in The Elderly in Korean.: Eun Jig Lee, Kyung Rae Kim, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Choon Hee Chung, Sung Kil Lim, Yoon Sok Chung; J Korean Endocr Soc. 1994;9(2):121-127. Published online November 6, 2019

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Abstract PDF: The seasonal variations in the parameters of calcium metabolism including 25-hydroxyvitamin D were analyzed in 19 free-living elderly subjects (mean age:68.7±6.7 yr) in Seoul. Mean serum total calcium concentration was 9.0±0.3 mg/dl in March and had risen to 9.3±0.3mg/dl in the following September(p<0.001). Despite their comparable calcium intake. Serum phosphorus and alkaline phosphatase concentrations did not show any seasonal variations, whereas serum PTH concentrations were significantly lower in September than in March(20.1±8.6 vs. 32.5±8.4 pg/ml, p<0.001). Seasonal changes in serum 25-hydroxyvitamin D concentrations were also found between the value(17.3±6.9 ng/ml) in March and that (28.5±7.4 ng/ml) in September(p<0.001). There was a significant correlation between seasonal increase in 25-hydroxyvitamin D and seasonal reduction in serum PTH/Cr(r=-0.5394, p<0.05). This study suggests that the winter minimum of serum 25-hydroxyvitamin D concentration and the elevated PTH may be a contributing risk factor for the development of osteopenia especially in the elderly individuals. When exposure to sunlight is reduced, as in the case of nursing home population, an additional exogenous form of the vitamin D may be advisable.

Bone Metabolism
Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis: In-Jin Cho, Ho-Yeon Chung, Sung-Woon Kim, Jae-Won Lee, Tae-Won Lee, Hye-Soon Kim, Sin-Gon Kim, Han Seok Choi, Sung-Hee Choi, Chan Soo Shin, Ki-Won Oh, Yong-Ki Min, Jung-Min Koh, Yumie Rhee, Dong-Won Byun, Yoon-Sok Chung, Jeong Hyun Park, Dong Jin Chung, Minho Shong, Eun-Gyoung Hong, Chang Beom Lee, Ki Hyun Baek, Moo-Il Kang; Endocrinol Metab. 2015;30(3):272-279. Published online December 9, 2014; DOI: https://doi.org/10.3803/EnM.2015.30.3.272

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Abstract PDF PubReader

Background

The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis.

Methods

This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period.

Results

After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment.

Conclusion

The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

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Review Articles

Bone Metabolism
Vitamin D Status in Korea: Han Seok Choi; Endocrinol Metab. 2013;28(1):12-16. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.12

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Abstract PDF PubReader

The majority of the vitamin D in our body is produced by cutaneous synthesis in response to sunlight. As more and more people live in cities and spend the bulk of their time indoors, it can be difficult to get sufficient sun exposure for adequate cutaneous production of vitamin D. Therefore, vitamin D insufficiency has become a very common health problem worldwide. The Korea National Health and Nutrition Examination Survey IV 2008 showed that the prevalence of vitamin D insufficiency, defined as a serum 25-hydroxyvitamin D [25(OH)D] level below 50 nmol/L, was 47.3% in males and 64.5% in females. Only 13.2% of males and 6.7% of females had a serum 25(OH)D level of greater than 75 nmol/L. In Korea, vitamin D insufficiency was more prevalent in young adults than in elderly people, likely due to the indoor lifestyle of younger people. Compared with the United States and Canada, Korea has a lower mean 25(OH)D level and a higher prevalence of vitamin D insufficiency. To improve the vitamin D status of the Korean population, more aggressive policies on food fortification and vitamin D supplementation are needed.

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Vitamin D: A D-Lightful Vitamin for Health.: Michael F Holick; Endocrinol Metab. 2012;27(4):255-267. Published online December 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.4.255

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Abstract PDF

Vitamin D is a sunshine vitamin that has been produced on this earth for more than 500 million years. Because foods contain so little vitamin D most humans have always depended on sun exposure for their vitamin D requirement. Vitamin D deficiency has been defined as a serum 25-hydroxyvitamin D concentration < 20 ng/mL (50 nmol/L); vitamin D insufficiency as a serum 25-hydroxyvitamin D of 21-29 ng/mL and vitamin D sufficiency as a serum 25-hydroxyvitamin D of 30-100 ng/mL whereas toxicity is usually not seen until blood levels are above 150 ng/mL. Vitamin D deficiency is a global health problem that increases risk for metabolic bone diseases in children and adults as well as many chronic illnesses including autoimmune diseases, type 2 diabetes, cardiovascular disease, infectious disease, and cancer. The major causes of vitamin D deficiency are lack of adequate sensible exposure to sunlight, inadequate dietary intake and obesity. The United States Endocrine Society recommended that to prevent vitamin D deficiency in those at risk, children 1 year and older require 600-1,000 international unit (IU) of vitamin D daily and adults require 1,500-2,000 IU of vitamin D daily. Obese patients require 2-3 times more vitamin D to both treat and prevent vitamin D deficiency.

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