many studies provide evidence pointing to a clear role of vitamin d in the pathogenesis of autoimmune diseases , especially autoimmune thyroid diseases ( aitds ) , as vitamin d deficiency is linked with high levels of anti - thyroid antibodies , abnormal thyroid function , increased thyroid volume , and increased tsh levels [ 14 ] .
nevertheless , at the present time vitamin d levels above 30  ng / ml are considered sufficient and confer protection from bone disease , whereas lower levels induce elevation of parathyroid hormone and are associated with other hazardous systemic effects . however , it is unclear whether low vitamin d levels are closely associated with the development of autoimmune thyroid disease .
some case - control studies have suggested that lower serum vitamin d levels or a higher prevalence of vitamin d insufficiency existed in patients with aitds compared with that in healthy controls [ 1 , 2 , 6 , 7 ] .
however , another study reported no significant association between serum vitamin d levels and thyroid autoimmunity .
thus , we aim to estimate the associations between vitamin d deficiency and/or insufficiency and autoimmune thyroid diseases , especially to clarify the relationship between vitamin d and serum thyroid autoantibody , in a relative rather than quantitative manner by comparing levels of vitamin d in a chinese population .
from may to june 2013 this study was performed in rmqi of xinjiang province . adults aged 16 years and above who were chinese citizens and lived in current residence for 3 years or longer were selected and invited into our study .
those with severe communication problems and acute illness and unwilling to participate were excluded from the study .
we excluded participants who had missing lab results ( n = 140 ) and questionnaire data ( n = 153 ) and were younger than 16 years old ( n = 4 ) and other ethnic groups ( n = 242 ) . finally , 1714 subjects were enrolled , including han and uyghur .
the study protocol was approved by the ethics committee of people 's hospital of xinjiang uyghur autonomous region .
informed consent was obtained from all subjects before data collection . in our study site ,
all the data collection was performed by the same staff group from department of endocrinology in people 's hospital of xinjiang uyghur autonomous region .
they were trained according to a standard protocol that made them familiar with the specific tools and methods used .
venous blood samples were drawn after an overnight fast of at least 8  h and centrifuged on the spot after collection .
serum 25(oh)d levels and thyroid parameters , serum tsh , and the levels of tgab and tpoab were measured with a roche electrochemiluminometric analyzer ( e601 ) , with an interassay variance of < 10% .
it is generally agreed that serum 25(oh)d levels of 20 to 30  ng / ml should be considered as representative of vitamin d insufficiency , whereas serum 25(oh)d levels of < 20  ng / ml should be considered as an indicative of vitamin d deficiency .
serum tpoab of > 35  iu / ml and/or tgab of > 116  iu / ml were considered autoantibody positivity ( roche ) .
continuous variables are presented as means  standard deviation for continuous normally distributed variables and median ( interquartile range ) for the nonnormally distributed variables .
student 's t - test and mann - whitney u test were used for comparison of mean values between groups .
linear regression analysis was used to examine the relationship between log - transformed tgab / tpoab titer and age , ethnicity , 25(oh)d , and other biochemical variables .
all calculations were performed using spss 19.0 for windows ( chicago , il , usa ) . a probability ( p ) value of < 0.05 was considered statistically significant for all tests .
a total of 1,714 subjects ( 969 han and 745 uyghur ) including 1,197 females ( 652 han and 545 uyghur ) and 517 males ( 317 han and 200 uyghur ) were enrolled in this study .
the mean level of total serum 25(oh)d was 16.55  8.53  ng / ml . vitamin d deficiency and insufficiency were noted in 1250 ( 72.9% ) and 344 ( 20.1% ) subjects , respectively .
females had higher serum tsh levels and tpoab and tgab titres but lower serum 25(oh)d levels than males ( p < 0.05 ) ( table 1 ) .
ethnic subgroup studies showed that uyghurs had higher tpoab and tgab titres but lower serum tsh and 25(oh)d levels compared to hans ( p  0.001 ) .
han subjects were significantly older than uyghurs ( 48.34  15.46 versus 43.78  12.81 years , p < 0.01 ) .
vitamin d insufficiency was noted in 28.3% of han and 9.3% of uyghur residents and vitamin d deficiency was seen in 61.6% of hans versus 87.6% of uyghurs . as shown in figure 2 , uyghurs had a lower mean 25(oh)d level compared to hans ( 19.40  8.37 versus 12.84  7.23 , p < 0.001 ) . in the ethnic han subgroup ,
females had a lower mean 25(oh)d level compared to males ( 19.18  8.88 versus 19.86  7.18  ng / ml , p = 0.002 ) ; similarly uyghur females had lower 25(oh)d levels than uyghur males ( 11.67  7.28 versus 16.04  6.01  ng / ml , p < 0.001 ) . in the present study , 240 ( 14.0% ) subjects were positive for serum tpoab and a total of 106 ( 6.2% ) subjects were positive for serum tgab , of which 209 ( 12.2% ) were positive for both serum tpoab and serum tgab .
there were a significant high proportion of females compared to males in tpo(+ ) , tg(+ ) , and tpo(+)tg(+ ) groups ( 73.3% versus 26.7% , p = 0.203 ; 85.8% versus 14.2% , p <
0.001 ; 86.6% versus 13.4% , p < 0.001 ; resp . ) , while the proportion of uyghurs was higher as compared to hans ( p < 0.05 ) only in the tg(+ ) group but not in the tpo(+ ) and tpo(+)tg(+ ) groups .
tgab(+ ) group had a lower mean 25(oh)d level compared to the tgab( ) group ( p < 0.01 ) .
the prevalence of vitamin d deficiency in tgab positive subjects was higher than that observed in tgab negative subjects , while no statistical difference was found ( 78.3% versus 72.6% , p = 0.199 ) .
the serum tsh levels in the tpo(+)tg(+ ) group were significantly higher than those in the tpo(+ ) group and tg(+ ) group ( p < 0.01 )
. however , there was no significant difference between tpo(+ ) group and tg(+ ) group ( table 2 ) . to account for the probable interaction between vitamin d status and anti - thyroid antibody level ,
it was found that higher tgab titres were associated with lower 25(oh)d levels independent of age , ethnicity , and tsh levels in females ( beta = 0.121 , p = 0.014 , table 3 ) but not in males .
linear regression analysis showed a weak relationship between tpoab titres and serum 25(oh)d levels independent of age , ethnicity , and tsh levels ( males , beta = 0.005 , p = 0.002 ; females , beta = 0.006 , p = 0.000 , table 4 ) .
age , tsh , and thyroid - globulin antibody titres , but not 25(oh)d or ethnicity , were associated with tpoab titres in men and women .
given the findings of lower serum 25(oh)d levels in female subjects in the tgab(+ ) group , we evaluated the adjusted odds ratios ( ors ) for women using multivariate logistic regression model .
the multivariate analysis using logistic regression revealed that 25(oh)d levels were an independent determinant of the presence of tgab ( odds ratio : 1.156 , 95% confidence interval : 1.0041.331 , p = 0.043 ; see table 5 ) after adjusting for age , gender , and ethnicity . in this analysis ,
in the current study , we found that a low circulating 25(oh)d level was significantly associated with a higher risk of prevalent aitds in females . to the best of our knowledge ,
this is the first study to investigate the association between circulating 25(oh)d and anti - thyroid antibodies in community based men and women from xinjiang province of china .
according to our study performed , the mean serum vitamin d level in the xinjiang population is 16.55  8.53  ng / ml , and the prevalence of vitamin d deficiency is 72.9% .
this prevalence is remarkably high in the uyghur population , especially in uyghur females compared to males . wearing covered clothing
the fact that vitamin d deficiency is predominantly found in uyghur females signifies a certain association between these two conditions ; it seems that the lower 25(oh)d level in uyghurs is due to headscarves and clothing that covers the neck , arms , and legs .
in contrast , han populations are more mindful of their health and often exercise outdoors before and after work and with ordinary clothing , thereby increasing their sunshine exposure .
lower vitamin d levels have been found in several autoimmune diseases , such as rheumatoid arthritis , systemic lupus erythematosus , systemic sclerosis , type 1 diabetes mellitus , multiple sclerosis , inflammatory bowel diseases , autoimmune thyroid diseases ( i.e. , hashimoto 's thyroiditis and graves ' disease ) , and autoimmune gastritis .
the mechanisms underlying the link between vitd and autoimmunity are not completely understood but probably are associated with its anti - inflammatory and immunomodulatory functions , as well as the presence of vdrs on most immune cells [ 10 , 11 ] .
aitds are multifactorial diseases in which autoimmunity plays a fundamental role with infiltration of the gland by t- and b - cells and production of specific autoantibodies , reactive to thyroid antigens [ antithyroglobulin , anti - thyroid peroxidase ( tpoab ) , and anti - tsh receptor ( trab ) ] .
.   reported , for the first time , a link between vitamin d deficiency and the presence of anti - thyroid antibodies . in recent years
, evidence has emerged pointing to an involvement of vitamin d in the development of autoimmune thyroid disease .
the immune modulator properties of vitamin d are ascribed to its effect on cells of the innate and adaptive systems , including macrophages , dendritic cells , and t and b lymphocytes , all of which harbor vdr .
recently , several genetic studies have demonstrated an association between thyroid autoimmunity susceptibility and gene polymorphisms of numerous proteins and enzymes that are associated with vitd functions , including vdr , dbp , cyp27b1 , and cyp2r1 [ 11 , 12 , 14 ] .
activated vitamin d modulates autoimmune reactions by regulating t lymphocytes to inhibit both the production and activity of cytokines .
vitamin d directly regulates t lymphocyte functions by inhibiting the proliferation of th1 cells and increasing the number of th2 cells .
vitamin d also suppresses the production of il-2 , il-5 , ifn - c , and tnf - a and increases the production of il-4 and transforming growth factor in th2 cells .
there are no further experimental studies to reveal whether there is a casual relationship and what are the mechanisms between low serum vitamin d and anti - thyroid antibody presence .
hence , from the results of our study , we supposed that vitamin d may enhance the responsiveness in thyroid autoimmune reaction which induced tgab secretion of thyrocytes . in the present study ,
the prevalence of vitamin d deficiency ( 78.3% ) and insufficiency ( 20% ) is higher in tgab positive subjects .
in addition , we explored the probable interaction between vitamin d status and thyroid - globulin antibodies in female xinjiang chinese population .
similar to the study in other populations , it has been observed that women have higher serum antithyroglobulin antibody ( tgab ) levels but lower serum 25(oh)d levels than men .
it is reported that vitamin d deficiency is more closely related to anti - thyroid antibody titer rather than thyroid function itself in humans .
our study not only supports the existing argument on the association between vitamin d and aitds but also further solidifies the association by revealing that 25(oh)d has a statistical correlation with tgab presence .
our current results suggest a possible crosstalk between vitamin d and x chromosome in the development of aitds .
the association of lower vitamin d levels with the higher prevalence of tgab positivity was found to be significant only in women and not in men , which is likely to more accurately reflect the mean reference value of serum 25(oh)d and the relationship with tgab .
aitds have a female  :  male ratio of approximately 9  :  1 .
there is also some studies that provide strong evidence for female predominance and x chromosome involvement in aitds , such as the finding that the x chromosome contains a considerable number of sex and immune - related genes that are essential in determining sex hormone levels and more importantly in immune tolerance , such as ar , il-2 receptor gamma chain , cd40 ligand , and foxp3 [ 2022 ] .
an alternative explanation has been recently proposed , that is , an enhanced skewed xci in peripheral blood cells of female patients with autoimmune diseases [ 2326 ] .
results from our study showed a significant high proportion of women in tg(+ ) group , which is consistent with previous studies , making better understanding of aitds occurrence risks from the perspective of sex determination genetics in females compared to males .
the x chromosome has been a recurrently suspicious contributor to disease genetics , and many reports provide strong evidence that the prevalence of vitamin d deficiency or insufficiency was more severe in female individuals .
further clinical and experimental investigations of the effect of vitamin d supplementation on thyroid antibodies , particularly in female individuals , are needed to elucidate an effect of vitamin d on either the thyrocytes or the thyroid follicular epithelium and genetic differences that might provide insight into this relationship .
most of the studies supported the inverse relation between low levels of 25(oh)d and autoimmune disease [ 1012 ] .
interestingly , in our study multivariate logistic regression analysis revealed that 25(oh)d was an independent risk factor of tgab . we suppose that this result of the study indicated that both low and high levels of vitamin d may result in an increased prevalence of autoimmune thyroid diseases .
some studies have investigated the association between mortality and higher levels of 25(oh)d and found both high and low levels of 25(oh)d were associated with increased risk of overall mortality [ 27 , 28 ] .
suggested a u - shaped relationship between serum 25(oh)d concentration and the frequency of certain pathologies .
unfortunately , the appropriate range for vitamin d that will be safe and sufficient to modulate immunological homeostasis is yet to be determined .
it is generally agreed that high serum 25(oh)d levels are associated with low circulating tsh . recently , population - based studies have reported that high vitamin d status in younger individuals and middle - aged and elderly males is associated with low circulating thyroid - stimulating hormone ( tsh ) [ 3 , 30 ] . however
, our study did not find a link between vitamin d status and thyrotropin after controlling for age , gender , ethnicity , and thyroid autoantibody .
the lack of statistical significance may be due to the relatively small number of subjects , especially after subgroup analysis in different ethnics or genders .
our study is limited by the fact that we did not record several factors affecting sun exposure , such as outdoor activity , difference in the use of sunscreens , and vacation activities . in our study ,
serum 25(oh)d was measured at the end of spring season in the xinjiang region of china ; the average amount of sunshine for may and june was up to 13 - 14 hours .
however , our findings strongly suggest that we likely underestimate vitamin d deficiency in the population .
another limitation is the lack of information on differences in socioeconomic status between hans and uyghurs in this cohort . besides , because of the cross - sectional nature of the present study ,
the causative effect of vitamin d on serum anti - thyroid - globulin antibody titres could not be readily determined .
25(oh)d status was much worse among uyghur ( especially in females ) populations , the prevalence of vitamin d deficiency and insufficiency was higher in tgab positive individuals , and low serum 25(oh)d was associated with tgab presence only in female subjects .
taken together , these data suggest a pathogenic relationship between vitamin d status and aitds .
future studies are warranted to clarify the potential contribution of the low serum vitamin d to the development of autoimmune thyroid diseases .
 
 objectives . some evidence has pointed out that vitamin d plays a significant role in reducing the incidence of autoimmune diseases , especially autoimmune thyroid diseases . 
 the authors aimed to examine the relationship between circulating 25-hydroxyvitamin d and thyroid autoantibody in a population - based health survey of xinjiang chinese population . subjects and methods . a total of 1714 chinese adults were analyzed . 
 25(oh)d , anti - thyroid antibodies , and thyroid function were measured . 
 results . 
 the prevalence of vitamin d insufficiency was 28.3% in hans and 9.3% in uyghurs , and the prevalence of vitamin d deficiency was 61.6% in hans and 87.6% in uyghurs . 
 overall prevalence of tgab positivity was 6.2% ( 0.9% males ; 5.3% females ) . 
 in female subjects , mean serum 25(oh)d levels were significantly lower in hans and uyghurs compared with males , and the difference was statistically significant . 
 importantly , after adjusting for age and ethnicity , a negative correlation ( r = 0.121 , p = 0.014 ) was recognized between 25(oh)d and tgab levels only in female subjects . 
 conclusion . 
 vitamin d insufficiency and deficiency are prevalent among chinese adults . 
 low serum 25(oh)d is related to the presence of tgab in females . 
 the causal effect of low vitamin d level on thyroid autoimmunity should be studied further more . 
1. Introduction
2. Subjects and Methods
3. Results
4. Discussion
5. Conclusion