Positive Association between Blood 25-Hydroxyvitamin D Levels and Pterygium after Control for Sunlight Exposure
Positive Association between Blood 25- Hydroxyvitamin D Levels and Pterygium after Control for Sunlight Exposure
Donghyun Jee 0 1
Eun Chul Kim 1
Eunyoung Cho 1 2
Jorge G. Arroyo 1
0 Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, Catholic University of Korea , Suwon , Korea , 2 Department of Ophthalmology and Visual Science , Bucheon St. Mary's Hospital, College of Medicine, Catholic University of Korea , Bucheon , Korea , 3 Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston , United States of America
1 Editor: Andrzej T Slominski, University of Alabama at Birmingham , UNITED STATES
2 Department of Dermatology, The Warren Alpert Medical School of Brown University, Providence, United States of America, 5 Department of Ophthalmology, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, Massachusetts , United States of America
To investigate the association between blood 25-hydroxyvitamin D levels and pterygium. Korean National Health and Nutrition Examination Survey 2008-2011 were used for the present epidemiologic study. A total of 19,178 participants aged for blood 25-hydroxyvitamin D levels and performed ophthalmic slit lamp examinations. Pterygium was considered as a growth of fibrovascular tissue over the cornea. The average blood 25-hydroxyvitamin D levels were 18.6 ng/mL, and prevalence of pterygium was 6.5%. The odds of pterygium significantly increased across blood 25-hydroxyvitamin D quintiles after controlling sun exposure time as well as other confounders such as sex, age, smoking, diabetes, hypertension (P < 0.001). The odds ratios (OR) for pterygium was 1.51 (95% Confidence Interval[95%CI]; 1.19-1.92) in the highest blood vitamin D quintile. Stratified analysis by sex showed a positive association between blood 25-hydroxyvitamin D levels and pterygium in both men (quintile 5 versus 1, OR; 1.68, 95%CI; 1.19-2.37) and women (quintile 5 versus 1, OR; 1.37, 95% CI; 1.00-1.88).
Funding: This research was supported by Basic
Science Research Program through the National
Research Foundation of Korea (NRF) funded by the
Even after controlling sun light exposure time, we found a positive association between
blood 25-hydroxyvitamin D levels and pterygium in a representative Korean population. The
mechanism underlying this association is unknown.
Pterygium is a benign uncontrolled growth of conjunctiva. It can significantly disturb the visual
function in advanced cases through irregular astigmatism, impaired tear film regularity, or
visual occlusion by a large pterygium over the visual axis. In addition, associated inflammation
can lead to conjunctival injection and ocular discomfort. Although the full pathophysiology of
pterygium is unclear, ultraviolet-mediated limbal damage is a risk factor for initiation of
]. In addition, the development of pterygium involves epidermal proliferation ,
inflammatory infiltration [
], angiosis and fibrosis [
], and alteration in the
epithelial-mesenchymal transition [
]. Recently, it has been reported that the S100 proteins, which are
calciumactivated signaling proteins, may be associated with the formation of pterygium [
tissue showed higher expression of S100 proteins than normal conjunctival tissue.
Vitamin D has not only function of calcium regulation but also other biologic functions
such as anti-inflammation or anti-oxidation [
]. Vitamin D was inversely associated with
chronic inflammation in many human studies [
]. Various ocular diseases including myopia
], age-related macular degeneration [
], and diabetic retinopathy [
] was found to be
related with vitamin D. Our previous work demonstrated that vitamin D was inversely related
with cataract , diabetic retinopathy [
], and age-related macular degeneration [
representative Korean population. In addition we reported no association between vitamin D and
dry eye syndrome, which implicated the differential effect of vitamin D on ocular diseases [
However, epidemiologic studies on the association between vitamin D levels and pterygium
are very limited. The results from our previous studies on the inverse association between
blood vitamin D and cataract and age-related macular degeneration [
] are interesting
considering that 90% of vitamin D is generated in the skin through sunlight, which has been
implicated as a risk factor for cataract and age-related macular degeneration [
the mechanism underlying pathogenesis of pterygium includes sunlight exposure as a risk
factor for pterygium [
]. Thus, blood vitamin D levels have the possibility playing a role in
pathogenesis of pterygium. In this study, the possible relationship between blood
25-hydroxyvitamin D levels and pterygium was evaluated in Korean adults. In addition, our
result for pterygium was compared to the results of our previous reports about association
between vitamin D and age-related macular degeneration, diabetic retinopathy, cataract, and
dry eye syndrome.
The study design followed the tenets of the Declaration of Helsinki for biomedical research.
Protocols for this study were approved by the institutional review board at the Catholic
University of Korea in Seoul. All participants provided written informed consent. We used data from
the Korean National Health and Nutrition Examination Survey (KNHANES). Details about
the study design and the methods used have been reported elsewhere [
]. KNHANES is a
nationwide and population-based cross-sectional study. For the present study, we included
data obtained from KNHANES 2008–2011. For the current study, 30,538 individuals who took
part in KNHANES were enrolled. Of these, 9,909 participants aged <30 years, 1,190
participants without blood 25-hydroxyvitamin D levels, and 1,190 participants without information
on the presence of pterygium were excluded from the study. Thus, 19,178 participants were
used in the final analysis (Fig 1).
The analysis of blood 25-hydroxyvitamin D levels has been described elsewhere [
radioimmunoassay kit (DiaSorin Inc., Stillwater, MN, USA) was used for measurement of
25-hydroxyvitamin D levels using a gamma counter (1470 Wizard, Perkin-Elmer, Finland),
followed by the standardization of vitamin D procedure . Blood samples were collected
2 / 10
Fig 1. Flow diagram showing the selection of study participants.
after an 8-h fast, and they were transported to a laboratory of the Neodin Medical Institute
after appropriate process. The measurement of 25-hydroxyvitamin D had the detection limit of
1.2 ng/ml. Interassay coefficients of variation were 2.8–6.2% for KNHANES 2008–2009, and
1.9–6.1% for for KNANES 2010–2011. A Hitachi 7600 clinical analyzer (Hitachi
High-Technologies Corporation, Tokyo, Japan) was used for measurement of other clinical variables
including total cholesterol, glucose, triglyceride and hemoglobin A1c levels.
The measurement of pterygium in KNHANES was documented in detail previously [
Briefly, slit-lamp eye examinations by a BQ 9001 (Haag-Streit AG; Koeniz, Switzerland) were
used for participants. Pterygium was defined as a growth of fibrovascular tissue over the
cornea. Other clinical and demographic characteristics were determined as follows. We calculated
body mass indices by dividing weight (kg) by height (m)2. Diabetes mellitus was considered to
be present when the subjects take anti-glycemic medication or a fasting blood-glucose level was
more than126 mg/dL. Hypertension was considered to be present when subjects take
3 / 10
antihypertensive medication or a systolic and diastolic blood pressure was more than 140
mmHg and 90 mmHg, respectively. Sunlight exposure time was evaluated by questionnaire
whether subjects have sunlight exposure more than 5 hours per day or not. Smoking status was
examined by questionnaire classifying participants into three categories: current, past, or non
The SPSS1 version 18.0 (SPSS, Chicago, IL, USA) were used for statistical analyses. Since
KNHANES used stratified, multistage sampling method, we incorporated sampling weights as
well as strata, sampling units in the statistical analysis. Continuous variables were presented
with the mean and standard error (SE), and categorical variables were presented with the
percentage and SE. To compare the patients’ demographic characteristics ANOVA or chi-square
tests were used. We used logistic regression analyses after categorization of 25-hydroxyvitamin
D levels into quintiles. To evaluate the confounding effect by confounders, we calculated three
odds ratio (OR); the crude OR (Model 1), age and sex adjusted OR (Model 2), and sex, age,
smoking, hypertension, diabetes, and sunlight exposure times adjusted OR (Model 3). We
tested multicollinearity, and exclude variables which has a variance inflation factor more than
5 for the logistic regression analyses. P values less than 0.05 were regarded as statistical
The average blood 25-hydroxyvitamin D levels were 18.6 ng/mL (SE, 0.1%). The prevalence of
pterygium in both genders was 6.5% (SE, 0.3%). The prevalence of pterygium was 6.8% (SE,
0.3%) in men and 6.3% (SE, 0.3%) in women. Table 1 showed that participants with pterygium
was significantly associated with old age, diabetes, hypertension, higher systolic blood pressure,
higher fasting glucose levels, higher 25-hydroxyvitamin D levels, and higher sun-exposure
times (P for all variables above < 0.001), compared with those without pterygium.
As quintiles of blood 25-hydroxyvitamin D levels, subjects had a tendency to be male
(P < 0.001), older (P < 0.001), hypertensive (P < 0.001), diabetic (P = 0.031), smoker
(P < 0.001), and have higher fasting glucose (P = 0.010), higher total cholesterol (P = 0.006),
and experienced longer sun exposures (P < 0.001, Table 2).
As the quintiles of the blood 25-hydroxyvitamin D levels increased, the odds of pterygium
significantly increased (P < 0.001). Even after controlling potential confounders mentioned
above, this positive association remained still strong and significant (P < 0.001, Table 3). OR
for pterygium in highest quintile of blood 25-hydroxyvitamin D levels over lowest one is 2.20
(P < 0.001, 95%CI; 1.75–2.77). After controlling potential confounders, OR for pterygium in
quintile 5 over quintile 1 is 1.51 (P < 0.001, 95%CI; 1.19–1.92, Fig 2). Stratified analysis by
gender demonstrated that after adjusting for potential confounders, the association between higher
blood 25-hydroxyvitamin D levels and the increasing odds of pterygium were significant both
in men (quintile 5 versus 1, OR; 1.68, 95% CI; 1.19–2.37,) and women (OR; 1.37, 95% CI; 1.00–
Our study is the first to evaluate the association between blood 25-hydroxyvitamin D levels
and pterygium. We found that even after adjusting for the sun light exposure time, the adjusted
odds of pterygium was associated with the increasing quintiles of the blood 25-hydroxyvitamin
D levels, and blood 25-hydroxyvitamin D levels were positively associated with of the
prevalence of pterygium. Based on this unexpected result we hypothesized that blood vitamin D
levels have an inverse association with the prevalence of pterygium.
4 / 10
(n = 261)
The exact mechanism underlying this relationship is unknown. One possible explanation is
that high vitamin D levels may elevate blood calcium levels and activate a calcium-activated
signaling protein, S100 protein, which has been implicated as a cause of pterygium development
]. Many pathophysiology in pterygium development including angiogenesis,
transdifferentiation, and cellular proliferation may be contributed to calcium signaling activities [
]. A recent in
vitro study demonstrated that calcium-free bathing medium made from blood reduced the
number of pterygium-derived fibroblasts, which is the main causal cell in pterygium development
]. In addition, suppressed calcium signaling activity reduced the growth rates of
pterygianderived fibroblasts [
]. It suggests that the calcium store plays important role in
pathophysiology of pterygian-derived fibroblasts. Thus, a higher level of vitamin D may elevate the cellular
calcium levels, which would enhance the calcium signaling development of pterygium through
S100 protein. However, we could not assess the blood calcium levels or S100 protein levels.
Further studies are required to identify the relationship between blood calcium levels and pterygium.
Another possible explanation is the residual confounding factor of sun exposure on the
association between vitamin D and pterygium. Because the majority of vitamin D is synthesized in the
skin from sunlight, the subjects with high blood vitamin D levels could have experienced longer
sun exposure times. Although we adjusted for sun exposure time in model 3, it is a dichotomous
variable ( 5 h or < 5 h/day). There is a possibility that sun exposure is a residual confounding
factor. However, the association between vitamin D and pterygium was consistently strong both
before and after adjusting for sun exposure time. Thus, it is unlikely that the residual
confounding factor of sun exposure time would cause the strong positive association between blood
5 / 10
vitamin D and pterygium. The contribution of sun exposure time is further supported by a
comparison of our results with the results of previous studies involving age-related macular
degeneration and cataract, in which sunlight exposure was an established risk factor [
We compared the association of pterygium with those for four other ocular diseases
(diabetic retinopathy, age-related macular degeneration, cataract, and dry eye syndrome) from our
previous reports which have used the same KNHANES population (Fig 3) [
]. The blood
vitamin D levels were inversely associated with the ocular diseases, although the strength of
association was different among the ocular diseases. In men, the ORs of late age-related
macular degeneration, diabetic retinopathy, cataract, and dry eye syndrome were 0.32 (95% CI,
0.12–0.81), 0.37 (95% CI, 0.18–0.76), 0.76 (95% CI, 0.59–0.99), and 0.85 (95% CI, 0.55–1.30),
respectively. However, in the present study, the blood vitamin D levels were positively
associated with pterygium (OR = 1.68, 95% CI = 1.19–2.37). Moreover, the association between
vitamin D and pterygium was stronger than those of other diseases, given that the relative odds of
pterygium in those with 3rd, 4th,and 5th vitamin D quintiles versus the lowest one were
significantly increased, whereas relative odds of other ocular diseases in those with only 5th vitamin
D quintile versus lowest one was significantly decreased. In addition, the association between
vitamin D and pterygium was shown in both men and women, whereas the association
between vitamin D and other ocular diseases has been shown only in men, not women. These
comparisons imply that the underlying mechanism of association between blood vitamin D
and pterygium may be different from those of the association between blood vitamin D and
other diseases (diabetic retinopathy, age-related macular degeneration, cataract, and dry eye
syndrome) in our previous reports [
The average vitamin D concentration (18.6 ng/mL) was low and in the range indicating
mild to moderate vitamin D insufficiency in clinical guidelines. These findings are supported
6 / 10
Prevalence was expressed as weighted estimates [%] (standard errors [%], 95% confidence intervals).
Model 1: Crude odds ratios. Model 2: adjusted for sex and age. Model 3: adjusted for sex, age, diabetes, hypertension, sunlight exposure time, smoking,
and body mass index.
* p < 0.05
Fig 2. The odds ratios of pterygium according to quintiles of blood vitamin D levels (reference
group = lowest vitamin D quintile group).
7 / 10
Fig 3. The comparison of odds ratios of ocular diseases including dry eye syndrome (DES), cataract,
agerelated macular degeneration (AMD), any diabetic retinopathy (DR), and vision-threatening DR (VTDR)
according to the blood vitamin D levels (reference group = lowest vitamin D quintile group).
by a previous study of Korea, in which prevalence of vitamin D insufficiency was 47.5% in
men, and 64.5% in women [
]. In addition, young adults aged 20–29 years showed the
prevalence of vitamin D insufficiency 65.0% in men and 79.9% in women. It implicates the vitamin
D insufficiency could be a greater threat to younger generation in Korea.
The present study has both strength and limitations. Strength is the large number of
participants in the present study. Another strength is the study’s design of nation-wide survey with
stratified, multi-clustered sampling. Limitation of this study is that seasonal variations of
vitamin D levels were not considered. Unfortunately, KNHANES does not have information on
sampling season. A recent study showed that an Asian population did not display any
significant seasonal variation in vitamin D status [
]. However, another study reported significant
seasonal variation with lower vitamin D levels in winter [
]. Another limitation is that our
study measured only 25-hydroxyvitamin D levels, which may not sufficient to reflect the body
vitamin D levels. The current dogma is that vitamin D is activated by 25-hydroxylation and
then 1,25-hydroxylation. Recently, novel pathways of vitamin D3 were found [
et al discovered the novel sequential hydroxylation that starts at carbon-20, which is initiated
] Predominant pathway is from vitamin D3 through 20-hydroxyvitamin
D to 20,23-hydroxyvitamin D. Finally, our study design is a cross-sectional study, which
introduced difficulties in reasoning causality.
In conclusion, our study is the first analysis of population-based epidemiologic data on the
association between blood 25-hydroxyvitamin D levels and pterygium. We found a positive
association between blood 25-hydroxyvitamin D levels and pterygium even after adjusting for
the confounder of sun light exposure time, which is contrary to the results of our previous
studies. The mechanism underlying this association is unknown and warrants further study.
Conceived and designed the experiments: DJ EK EC JA. Performed the experiments: DJ EK EC
JA. Analyzed the data: DJ EK EC JA. Contributed reagents/materials/analysis tools: DJ EK EC.
Wrote the paper: DJ EK.
8 / 10
9 / 10
1. Coroneo MT . Pterygium as an early indicator of ultraviolet insolation: a hypothesis . Br J Ophthalmol . 1993 ; 77 ( 11 ): 734 - 9 . Epub 1993/11/01. PMID: 8280691; PubMed Central PMCID : PMCPmc504636 .
2. Coroneo MT , Di Girolamo N , Wakefield D. The pathogenesis of pterygia . Curr Opin Ophthalmol . 1999 ; 10 ( 4 ): 282 - 8 . Epub 2000/01/06. PMID: 10621537 .
3. Tan DT , Liu YP , Sun L . Flow cytometry measurements of DNA content in primary and recurrent pterygia . Invest Ophthalmol Vis Sci . 2000 ; 41 ( 7 ): 1684 - 6 . Epub 2000/06/14. PMID: 10845586 .
4. Di Girolamo N , Wakefield D , Coroneo MT . UVB-mediated induction of cytokines and growth factors in pterygium epithelial cells involves cell surface receptors and intracellular signaling . Invest Ophthalmol Vis Sci . 2006 ; 47 ( 6 ): 2430 - 7 . Epub 2006/05/26. doi: 10 .1167/iovs.05-1130 PMID: 16723453 .
5. Liu T , Liu Y , Xie L , He X , Bai J . Progress in the pathogenesis of pterygium . Curr Eye Res . 2013 ; 38 ( 12 ): 1191 - 7 . Epub 2013/09/21. doi: 10 .3109/02713683. 2013 .823212 PMID: 24047084 .
6. Chui J , Di Girolamo N , Wakefield D , Coroneo MT . The pathogenesis of pterygium: current concepts and their therapeutic implications . The ocular surface . 2008 ; 6 ( 1 ): 24 - 43 . Epub 2008/02/12. PMID: 18264653 .
7. Riau AK , Wong TT , Beuerman RW , Tong L . Calcium-binding S100 protein expression in pterygium . Molecular Vision . 2009 ; 15 : 335 - 42 . PMID: PMC2642841 .
8. Alvarez JA , Chowdhury R , Jones DP , Martin GS , Brigham KL , Binongo JN , et al. Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulfide redox status in adults . Clinical endocrinology . 2014 . Epub 2014/03/19. doi: 10 .1111/cen.12449 PMID: 24628365 .
9. Uberti F , Lattuada D , Morsanuto V , Nava U , Bolis G , Vacca G , et al. Vitamin D protects Human Endothelial Cells from oxidative stress through the autophagic and survival pathways . The Journal of clinical endocrinology and metabolism . 2013:jc20132103. Epub 2013 /11/29. doi: 10 .1210/jc.2013-2103 PMID: 24285680 .
10. Mangge H , Weghuber D , Prassl R , Haara A , Schnedl W , Postolache TT , et al. The Role of Vitamin D in Atherosclerosis Inflammation Revisited: More a Bystander than a Player? Current vascular pharmacology . 2013. Epub 2013 /12/18. PMID: 24329737 .
11. Grant W , Strange R , Garland C . Sunshine is good medicine. The health benefits of ultraviolet‐B induced vitamin D production . Journal of cosmetic dermatology . 2003 ; 2 ( 2 ): 86 - 98 . PMID: 17156062
12. Choi JA , Han K , Park YM , La TY. Low Serum 25- Hydroxyvitamin D Is Associated with Myopia in Korean Adolescents . Invest Ophthalmol Vis Sci . 2014 . Epub 2014/02/01. doi: 10 .1167/iovs.13-12853 PMID: 24481261 .
13. Parekh N , Chappell RJ , Millen AE , Albert DM , Mares JA . Association between vitamin D and agerelated macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994 . Arch Ophthalmol . 2007 ; 125 ( 5 ): 661 - 9 . Epub 2007/05/16. doi: 10 .1001/archopht.125.5. 661 PMID: 17502506 .
14. Payne JF , Ray R , Watson DG , Delille C , Rimler E , Cleveland J , et al. Vitamin D insufficiency in diabetic retinopathy . Endocrine Practice . 2012 ; 18 ( 2 ): 185 - 93 . doi: 10 .4158/EP11147.OR PMID: 21940279
15. Patrick PA , Visintainer PF , Shi Q , Weiss IA , Brand DA . Vitamin D and retinopathy in adults with diabetes mellitus . Arch Ophthalmol . 2012 ; 130 ( 6 ): 756 - 60 . Epub 2012/07/18. doi: 10 .1001/archophthalmol. 2011 .2749 PMID: 22801837 .
16. Jee D , Kim EC . Association between serum 25-hydroxyvitamin D levels and age-related cataracts . Journal of cataract and refractive surgery . 2015 ; 41 ( 8 ): 1705 - 15 . Epub 2015/10/04. doi: 10 .1016/j.jcrs. 2014 . 12 .052 PMID: 26432129 .
17. Jee D , Han K , Kim EC . Inverse association between high blood 25-hydroxyvitamin D levels and diabetic retinopathy in a representative Korean population . PLoS One . 2014 ; 9 ( 12 ): e115199 . Epub 2014 / 12/09. doi: 10 .1371/journal.pone.0115199 PMID: 25485770; PubMed Central PMCID : PMCPmc4259490 .
18. Kim EC , Han K , Jee D. Inverse Relationship between High Blood 25-Hydroxyvitamin D and Late Stage of Age-Related Macular Degeneration in a Representative Korean Population . Invest Ophthalmol Vis Sci . 2014 . Epub 2014/07/13. doi: 10 .1167/iovs.14-14763 PMID: 25015360 .
19. Jee D , Kang S , Yuan C , Cho E , Arroyo JG . Serum 25- Hydroxyvitamin D Levels and Dry Eye Syndrome: Differential Effects of Vitamin D on Ocular Diseases . PLoS One . 2016 ; 11 ( 2 ): e0149294 . Epub 2016 /02/ 20. doi: 10 .1371/journal.pone.0149294 PMID: 26894581 .
20. Sui GY , Liu GC , Liu GY , Gao YY , Deng Y , Wang WY , et al. Is sunlight exposure a risk factor for agerelated macular degeneration? A systematic review and meta-analysis . Br J Ophthalmol . 2013 ; 97 ( 4 ): 389 - 94 . Epub 2012/11/13. doi: 10 .1136/bjophthalmol-2012 -302281 PMID: 23143904.
21. Roberts JE . Ultraviolet radiation as a risk factor for cataract and macular degeneration . Eye & contact lens . 2011 ; 37 ( 4 ): 246 - 9 . Epub 2011/05/28. doi: 10 .1097/ICL.0b013e31821cbcc9 PMID: 21617534 .
22. Lucas RM . An epidemiological perspective of ultraviolet exposure-public health concerns . Eye & contact lens . 2011 ; 37 ( 4 ): 168 - 75 . Epub 2011/06/15. doi: 10 .1097/ICL.0b013e31821cb0cf PMID: 21670693 .
23. Chalam KV , Khetpal V , Rusovici R , Balaiya S. A review: role of ultraviolet radiation in age-related macular degeneration . Eye & contact lens . 2011 ; 37 ( 4 ): 225 - 32 . Epub 2011/06/08. doi: 10 .1097/ICL. 0b013e31821fbd3e PMID: 21646979 .
24. Kim Y , Park S , Kim NS , Lee BK . Inappropriate survey design analysis of the Korean National Health and Nutrition Examination Survey may produce biased results . Journal of preventive medicine and public health = Yebang Uihakhoe chi . 2013 ; 46 ( 2 ): 96 - 104 . Epub 2013/04/11. doi: 10 .3961/jpmph. 2013 . 46 . 2.96 PMID: 23573374; PubMed Central PMCID : PMCPmc3615385 .
25. Park HA . The Korea national health and nutrition examination survey as a primary data source . Korean journal of family medicine . 2013 ; 34 ( 2 ): 79 . Epub 2013/04/06. doi: 10 .4082/kjfm. 2013 . 34 .2.79 PMID: 23560205; PubMed Central PMCID : PMCPmc3611106 .
26. Eum K-D , Lee M-S , Paek D. Cadmium in blood and hypertension . Science of the Total Environment . 2008 ; 407 ( 1 ): 147 - 53 . doi: 10 .1016/j.scitotenv. 2008 . 08 .037 PMID: 18845316
27. Lee M-S , Park SK , Hu H , Lee S . Cadmium exposure and cardiovascular disease in the 2005 Korea National Health and Nutrition Examination Survey . Environmental research . 2011 ; 111 ( 1 ): 171 - 6 . doi: 10 .1016/j.envres. 2010 . 10 .006 PMID: 21055738
28. Sempos CT , Vesper HW , Phinney KW , Thienpont LM , Coates PM . Vitamin D status as an international issue: national surveys and the problem of standardization . Scandinavian journal of clinical and laboratory investigation Supplementum . 2012 ; 243 : 32 - 40 . Epub 2012/06/08. doi: 10 .3109/00365513. 2012 . 681935 PMID: 22536760 .
29. Rim TH , Nam J , Kim EK , Kim TI . Risk factors associated with pterygium and its subtypes in Korea: the Korean National Health and Nutrition Examination Survey 2008-2010 . Cornea. 2013 ; 32 ( 7 ): 962 - 70 . Epub 2013/02/28. doi: 10 .1097/ICO.0b013e3182801668 PMID: 23442251 .
30. Fang C , Illingworth CD , Qian L , Wormstone IM . Serum deprivation can suppress receptor-mediated calcium signaling in pterygial-derived fibroblasts . Invest Ophthalmol Vis Sci . 2013 ; 54 ( 7 ): 4563 - 70 . Epub 2013/06/14. doi: 10 .1167/iovs.13-11604 PMID: 23761089 .
31. Choi HS , Oh HJ , Choi H , Choi WH , Kim JG , Kim KM , et al. Vitamin D insufficiency in Korea-a greater threat to younger generation: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008 . The Journal of clinical endocrinology and metabolism . 2011 ; 96 ( 3 ): 643 - 51 . Epub 2010/12/31. doi: 10 .1210/jc.2010-2133 PMID: 21190984 .
32. Smith M. Seasonal , ethnic and gender variations in serum vitamin D3 levels in the local population of Peterborough . Bioscience Horizons . 2010 ; 3 ( 2 ): 124 - 31 .
33. Lee YA , Kim HY , Hong H , Kim JY , Kwon HJ , Shin CH , et al. Risk factors for low vitamin D status in Korean adolescents: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008 - 2009 . Public health nutrition . 2014 ; 17 ( 4 ): 764 - 71 . Epub 2013/03/07. doi: 10 .1017/ s1368980013000438 PMID: 23462341 .
34. Slominski A , Semak I , Zjawiony J , Wortsman J , Li W , Szczesniewski A , et al. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism . The FEBS journal . 2005 ; 272 ( 16 ): 4080 - 90 . doi: 10 .1111/j.1742- 4658 . 2005 . 04819 . x PMID : PMC2234577 .
35. Slominski AT , Li W , Kim TK , Semak I , Wang J , Zjawiony JK , et al. Novel activities of CYP11A1 and their potential physiological significance . J Steroid Biochem Mol Biol . 2015 ; 151 : 25 - 37 . Epub 2014/12/ 03. doi: 10 .1016/j.jsbmb. 2014 . 11 .010 PMID: 25448732; PubMed Central PMCID : PMCPMC4757911 .
36. Slominski AT , Kim T-K , Li W , Postlethwaite A , Tieu EW , Tang EKY , et al. Detection of novel CYP11A1- derived secosteroids in the human epidermis and serum and pig adrenal gland . Scientific Reports . 2015 ; 5 : 14875 . doi: 10 .1038/srep14875 PMID: PMC4597207 .
37. Slominski AT , Kim TK , Shehabi HZ , Semak I , Tang EK , Nguyen MN , et al. In vivo evidence for a novel pathway of vitamin D(3) metabolism initiated by P450scc and modified by CYP27B1 . FASEB journal: official publication of the Federation of American Societies for Experimental Biology . 2012 ; 26 ( 9 ): 3901 - 15 . Epub 2012/06/12. doi: 10 .1096/fj.12-208975 PMID: 22683847; PubMed Central PMCID : PMCPMC3425822 .
38. Slominski AT , Kim TK , Chen J , Nguyen MN , Li W , Yates CR , et al. Cytochrome P450scc-dependent metabolism of 7-dehydrocholesterol in placenta and epidermal keratinocytes . The international journal of biochemistry & cell biology . 2012 ; 44 ( 11 ): 2003 - 18 . Epub 2012/08/11. doi: 10 .1016/j.biocel. 2012 . 07 . 027 PMID: 22877869; PubMed Central PMCID : PMCPMC3520099 .