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The C-variant of a T-13910C polymorphism (rs4988235; NT_022135.15:g.25316568G > A) upstream of the lactase phlorizin hydrolase (LPH) gene causes lactose intolerance. Association studies with differences in bone parameters and fracture risk have been inconclusive. The objective of this study was to examine the association of LPH rs4988235 with body...
Contexts in source publication
Context 1
... no consistent results in epidemiologic studies have been found. Table 1 summarizes the outcome of several studies that assessed lactose intolerance with BMD and/or fracture risk in countries with high (Finland) or low (Austria) calcium intake. (7)(8)(9)(10)(11) The vitamin D receptor (VDR) gene mediates the actions of the vitamin D endocrine system in calcium homeostasis and bone metabolism. ...
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... intake and energy intake were not different between the different genotypes. Most other studies that assessed the relationship between genetically defined lactose intolerance and calcium intake did show significantly lower calcium intake from milk but not lower overall dietary calcium intake (Table 1). In a group of young Finnish men, total dietary calcium intake was similar for the three different genotypes, although calcium intake from milk and yogurt was lowest for the C-homozygotes. ...
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... In addition, the overall calcium intake in several independent studies in Austria was approximately 600 g/day, which is about half the Dutch daily calcium intake. (10) Studies that have investigated the influence of lactose intolerance in relation to bone (Table 1) are conflicting and inconclusive. Differences in prevalence, as well as social and cultural differences between populations, might have contrib- uted to this, and selection criteria for the inclusion of participants may have diluted or enhanced associations. ...
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... no consistent results in epidemiologic studies have been found. Table 1 summarizes the outcome of several studies that assessed lactose intolerance with BMD and/or fracture risk in countries with high (Finland) or low (Austria) calcium intake. (7)(8)(9)(10)(11) The vitamin D receptor (VDR) gene mediates the actions of the vitamin D endocrine system in calcium homeostasis and bone metabolism. ...
Context 5
... intake and energy intake were not different between the different genotypes. Most other studies that assessed the relationship between genetically defined lactose intolerance and calcium intake did show significantly lower calcium intake from milk but not lower overall dietary calcium intake (Table 1). In a group of young Finnish men, total dietary calcium intake was similar for the three different genotypes, although calcium intake from milk and yogurt was lowest for the C-homozygotes. ...
Context 6
... In addition, the overall calcium intake in several independent studies in Austria was approximately 600 g/day, which is about half the Dutch daily calcium intake. (10) Studies that have investigated the influence of lactose intolerance in relation to bone (Table 1) are conflicting and inconclusive. Differences in prevalence, as well as social and cultural differences between populations, might have contributed to this, and selection criteria for the inclusion of participants may have diluted or enhanced associations. ...
Citations
... For the present work, the SNPs identified by GEFOS/ GENOMOS in previous GWAS analyses 26 with the ultimate objective of constructing a genetic risk score (GRS) that can help to identify individuals at the extremes of the fracture risk distribution (i.e., and very high or very low risk of fracture) as well as an established Caucasian lactose intolerance marker were chosen to be detected. 66 The subsets of SNPs are included in Table 1 and are referred to as SNP 10 (rs10457487), SNP 27 (rs2741856), SNP 29 (rs2908007), SNP 46 (rs4635400), and SNP 49 (rs4988235). ...
Osteoporosis is a multifactorial disease influenced by genetic and environmental factors, which contributes to an increased risk of bone fracture, but early diagnosis of this disease cannot be achieved using current techniques. We describe a generic platform for the targeted electrochemical genotyping of SNPs identified by genome-wide association studies to be associated with a genetic predisposition to osteoporosis. The platform exploits isothermal solid-phase primer elongation with ferrocene-labeled nucleoside triphosphates. Thiolated reverse primers designed for each SNP were immobilized on individual gold electrodes of an array. These primers are designed to hybridize to the SNP site at their 3'OH terminal, and primer elongation occurs only where there is 100% complementarity, facilitating the identification and heterozygosity of each SNP under interrogation. The platform was applied to real blood samples, which were thermally lysed and directly used without the need for DNA extraction or purification. The results were validated using Taqman SNP genotyping assays and Sanger sequencing. The assay is complete in just 15 min with a total cost of 0.3€ per electrode. The platform is completely generic and has immense potential for deployment at the point of need in an automated device for targeted SNP genotyping with the only required end-user intervention being sample addition.
... Furthermore, young adults with lactase deficiency exhibited elevated parathormone (PHT) levels [64]. Koek et al. [65] demonstrated a clear relationship between dietary calcium intake and serum ionized calcium levels. However, Yahya et al. [66] showed that, although young Malaysian adults had a high prevalence of ATH, there was no direct effect on bone health, unlike calcium intake, which was low. ...
Intolerance to dairy products resulting from the abnormal digestion of milk sugar (lactose) is a common cause of human gastrointestinal disorders. The aim of this study was to show that the-13910 C>T LCT gene polymorphism, together with genotypes of selected VDR gene polymorphisms and diet and nutritional status parameters, can impact the prevalence of vitamin D and calcium deficiency in young adults. This study was conducted on a group of 63 people, which comprised 21 individuals with primary adult lactase deficiency, and a control group of 42 individuals with no hypolactasia. The LCT and VDR gene genotypes were assessed using PCR restriction fragment length polymorphism (PCR-RFLP) analysis. A validated HPLC method was used to determine serum concentrations of 25(OH)D 2 and 25(OH)D 3. Atomic absorption spectrometry was used to determine calcium levels. Their diets (self-reported 7-day estimated food record), estimated calcium intakes based on the ADOS-Ca questionnaire and basic anthropometric parameters were assessed. The CC genotype associated with hypolactasia was found in 33.3% of the subjects. The presence of the CC variant of the LCT gene polymorphism in the study group of young Polish adults was found to be associated with significantly lower milk (134.7 ± 66.7 g/d vs. 342.5 ± 176 g/d; p = 0.012) and dairy product consumption (78.50 ± 36.2 g/d vs. 216.3 ± 102 g/d; p = 0.008) compared with lactase persistence. At the same time, people with adult-type primary intolerance were found to have statistically significant lower serum levels of vitamin D and calcium (p < 0.05). There was a higher chance of vitamin D and calcium deficiency and a lower intake in the group exhibiting lactase non-persistence (OR > 1). The AA variant of the VDR gene's BsmI polymorphism present in people with hypolactasia may further contribute to an increased risk of vitamin D deficiency. Exclusion of lactose from the diet, combined with impaired vitamin D metabolism, may also lead to inhibited calcium absorption by the body. Further research should be carried out on a larger group of subjects to clarify the relationship between lactase activity and vitamin D and calcium levels in young adults.
... We assessed the quality of included studies using the Q-Genie tool (Table 1). Nineteen studies (46%) were of good quality [9,12,19,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], 16 studies (39%) of moderate quality [8,11,13,[39][40][41][42][43][44][45][46][47][48][49][50][51] and six studies (15%) of poor quality [10,[52][53][54][55][56]. Most studies sufficiently provided a rational for the selected gene or genes in the study and appropriately drew conclusions supported by the presented results. ...
... Studies were carried out between 1999 [13,40,49] and 2019 [9,35]. Twenty-one studies were conducted in Europe [8,10,11,[26][27][28][29][30][31][32][33]38,39,[42][43][44][49][50][51][52]54], 10 in Asia [12,24,36,37,45,47,48,53,55,56] and six in North America [13,19,23,25,40,41]. Three studies [9,34,35] included cohorts from different countries while one study provided no country information [46]. ...
... Three studies [9,34,35] included cohorts from different countries while one study provided no country information [46]. Of the included studies, 17 were cross-sectional studies [8,11,13,27,30,33,34,[37][38][39]41,45,[49][50][51]53,56], 14 were case-control studies [10,12,19,24,29,31,32,36,42,43,47,48,52,55], seven association studies [23,25,26,35,40,46,54] and three were Mendelian randomisation studies [9,28,44]. Twenty-six studies examined the association between calcium and polymorphisms in the CASR gene (Table 2). ...
This systematic review assessed genotypes and changes in calcium homeostasis. A literature search was performed in EMBASE, Medline and CENTRAL on 7 August 2020 identifying 1012 references. Studies were included with any human population related to the topic of interest, and genetic variations in genes related to calcium metabolism were considered. Two reviewers independently screened references, extracted relevant data and assessed study quality using the Q-Genie tool. Forty-one studies investigating Single Nucleotide Polymorphisms (SNPs) in relation to calcium status were identified. Almost half of the included studies were of good study quality according to the Q-Genie tool. Seventeen studies were cross-sectional, 14 case-control, seven association and three were Mendelian randomization studies. Included studies were conducted in over 18 countries. Participants were mainly adults, while six studies included children and adolescents. Ethnicity was described in 31 studies and half of these included Caucasian participants. Twenty-six independent studies examined the association between calcium and polymorphism in the calcium-sensing receptor (CASR) gene. Five studies assessed the association between polymorphisms of the Vitamin D receptor (VDR) gene and changes in calcium levels or renal excretion. The remaining ten studies investigated calcium homeostasis and other gene polymorphisms such as the CYP24A1 SNP or CLDN14. This study identified several CASR, VDR and other gene SNPs associated with calcium status. However, to provide evidence to guide dietary recommendations, further research is needed to explore the association between common polymorphisms and calcium requirements.
... In this sense, numerous studies have reported the significant role of the LCT -13910C>T polymorphism in osteoporosis, where the CC genotype has been associated with the decrease of BMD at different sites and the predisposition to bone fractures (Obermayer-Pietsch et al., 2004;Laaksonen et al., 2009;Bácsi et al., 2009;Marozik et al., 2013). However, this is still a matter of debate since, in other studies, non-significant relationship was found (Enattah et al., 2004Obermayer-Pietsch et al., 2007;Gugatschka et al., 2007;Esterle et al., 2009;Kull et al., 2009;Smith et al., 2009;Agueda et al., 2010;Koek et al., 2010;Tolonen et al., 2011;Bergholdt et al., 2018). Table 1 summarizes the studies that assessed LCT -13910C>T polymorphism with BMD and/or fracture risk in Europe. ...
... traits, like BMD and/or fractures, in a cohort of 964 Spanish postmenopausal women. Moreover, no associations were found in several studies for different cohorts and populations, such as Finland (Tolonen et al., 2011;Enattah et al., 2004, Austria (Obermayer-Pietsch et al., 2007;Gugatschka et al., 2007), France (Esterle et al., 2009), Estonia (Kull et al., 2009), United Kingdom (Smith et al., 2009), Netherlands (Koek et al., 2010), and Denmark (Bergholdt et al., 2018) ( Table 1). In all these studies, the frequency of LNP individuals varied from 6.80% (Smith et al., 2009) to 43.84% (Obermayer-Pietsch et al., 2007) (Table 1). ...
Hip fracture is a common health problem very frequent in the older adult population and is associated with significant morbidity, mortality, and societal costs. There are several factors that increase the risk of suffering a hip fracture, however, the effect of genetic lactase non-persistence is not clear-cut yet. For this reason, we investigated if the LCT -13910C>T polymorphism is a potential risk factor for osteoporotic hip fractures in older adult people from the Northern Spain population. A total of 740 individuals were included in this study. Of them, 364 belonged to the group of patients whit osteoporotic hip fracture while the control group consisted of 376 individuals without hip fracture. The genotypes for the LCT -13910C>T polymorphism were analyzed by using polymerase chain reaction and high resolution melting. The prevalence of the CC genotype, which is related to lactase non-persistence, did not differ significantly in both groups. Likewise, no differences were observed between groups when they were compared with regard to the C or the T allele, or when they were analyzed considering gender. Additionally, our results were compared with those obtained in a control group of 207 nonagenarian individuals originally from Northern Spain and no differences were observed. In conclusion, no significant association was observed between the LCT -13910C>T polymorphism and the risk for suffering hip fracture in the older adult population of Northern Spain.
... W. Koek и соавт. (2010) [36] в дополнение к антропометрическому показателю роста, состоянию минеральной плотности костной ткани и кальциевому гомеостазу провели анализ взаимосвязи наличия полиморфизма рецепторов витамина D (VDR) у пожилых людей с различными генотипами гена LCT. Данный анализ не выявил ассоциаций у пожилых лиц, принадлежащих к разным генотипам, с минеральной плотностью шейки бедренной кости и поясничного отдела позвоночника, а также с риском переломов. ...
... Ни для одного из изученных параметров не наблюдалось взаимодействия между полиморфизмами 13910T>C и гаплотипом VDR block 51. В результате исследования установлено, что аллель С указанного полиморфизма, вызывающий непереносимость лактозы, связан с более низким употреблением кальция с пищей и уровнем кальция в сыворотке крови, но не с минеральной плотностью костной ткани или переломами [36]. ...
Lactose (β-galactosyl-1,4 glucose) is milk sugar, the main disaccharide of human and other mammalian breast milk. Lactase is intestinal disaccharidase that catalyzes the lactose hydrolysis. The lactase gene LCT controls biological function of the enzyme. The age-related genetically determined feature of disaccharide expression, epigenetic factors, and natural selection with persistent tolerance to milk sugar throughout lifetime has divided the human population according to the LCT gene into two phenotypes: lactase persistent and lactase non-persistent. There is conflicting evidence that the latter phenotype is associated with low calcium absorption and the development of osteoporosis. The regular use of fermented probiotic dairy products by individuals with the lactase non-persistence phenotype ensures the accumulation of peak bone mineralization and prevents osteoporosis.
... 22 The well established lactose intolerance marker (LCT (C/T-13910) polymorphism; rs4988235) 30 was used as a surrogate to assess long term differences in dairy derived calcium intake. 31 Additional risk factors were considered for inclusion; however, at the time of analyses, well powered GWAS were not available for some risk factors of interest including alcohol intake, 32 33 smoking 34 and plasma calcium levels. 35 Body mass index 36 was not evaluated given that the fracture discovery analysis was adjusted for body weight and height. ...
Objectives
To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk.
Design
Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach.
Setting
25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data.
Participants
A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor.
Results
Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10⁻⁶⁸). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture.
Conclusions
This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.
... Most of clinical studies focused on postmenopausal women and elderly men. In result, several authors reported significant association of LCT genotypes and BMD [4][5][6], while others have failed to confirm this relation [7,8]. It was also observed that LI/LT influenced reaching the peak of bone mass (PBM) in young adults [4]. ...
The relation of LCT-13910 genotypes and bone mineral density (BMD) has been the subject of modern-day human population studies, giving inconsistent results. In the present study we analyze for the first time a relation of LCT-13910 genotypes and BMD in historical skeletal individuals. Ancient population might be a model for testing this association due to elimination of non-natural factors affecting bone density. Among 22 medieval individuals from Sanok churchyard (South-Eastern Poland; dated from XIV to XVII c. AD) we identified 4 individuals with osteoporosis (mean BMD = 0.468 g/cm 2 , SD = 0.090), 10 individuals with osteo-penia (mean BMD = 0.531 g/cm 2 , SD = 0.066) and 8 individuals with normal BMD values (mean BMD = 0,642 g/cm 2 , SD = 0.060). Analyses of BMD and LCT-13910 genotypes revealed that mean BMD was the highest (0.583 g/cm 2 , SD = 0.065) in the individuals with lactose tolerance genotypes (TT and CT). We also found possible association of lower BMD at the radius and CC genotypes due to higher but not statistically significant frequency of osteoporosis in the lactose intolerant group (p = 0.60). Statistically significant correlation was found between BMD and females aged 20-35 years, with tendency to reduce BMD with age (p = 0.02).
... Since then, several studies regarding the association between LCT (C/T-13910) polymorphism and bone density and fracture were published. However, the results were inconsistent (Enattah et al. 2005a, b;Gugatschka et al. 2007;Obermayer-Pietsch et al. 2007;Bácsi et al. 2009;Kull et al. 2009;Smith et al. 2009;Agueda et al. 2010;Koek et al. 2010;Marozik et al. 2013). Presently, there is no meta-analysis focussed on the relationship between LCT 13910 C/T gene polymorphism and bone density and fracture risk across different studies. ...
... For BMD phenotypes, nine studies from seven articles analysed BMD of femoral neck (Enattah et al. 2004;Obermayer-Pietsch et al. 2004Kull et al. 2009;Agueda et al. 2010;Koek et al. 2010;Marozik et al. 2013), and eight studies from seven articles analysed BMD of lumbar spine (Enattah et al. 2004;Obermayer-Pietsch et al. 2004Kull et al. 2009;Agueda et al. 2010;Koek et al. 2010;Marozik et al. 2013). For fracture, seven studies from seven articles analysed fracture at any site (Obermayer-Pietsch et al. 2004Enattah et al. 2005a, b;Bácsi et al. 2009;Smith et al. 2009;Agueda et al. 2010), and four studies from four articles analysed vertebral fracture (Enattah et al. 2004;Obermayer-Pietsch et al. 2007;Bácsi et al. 2009;Agueda et al. 2010). ...
... For BMD phenotypes, nine studies from seven articles analysed BMD of femoral neck (Enattah et al. 2004;Obermayer-Pietsch et al. 2004Kull et al. 2009;Agueda et al. 2010;Koek et al. 2010;Marozik et al. 2013), and eight studies from seven articles analysed BMD of lumbar spine (Enattah et al. 2004;Obermayer-Pietsch et al. 2004Kull et al. 2009;Agueda et al. 2010;Koek et al. 2010;Marozik et al. 2013). For fracture, seven studies from seven articles analysed fracture at any site (Obermayer-Pietsch et al. 2004Enattah et al. 2005a, b;Bácsi et al. 2009;Smith et al. 2009;Agueda et al. 2010), and four studies from four articles analysed vertebral fracture (Enattah et al. 2004;Obermayer-Pietsch et al. 2007;Bácsi et al. 2009;Agueda et al. 2010). ...
A number of studies have investigated the association of lactase (LCT, C/T-13910) gene polymorphism with bone mineral density (BMD) and fracture risk, but previous results were inconclusive. In this study, a meta-analysis was performed to quantify the association of LCT (C/T-13910) polymorphism with BMD and fracture risk. Eligible publications were searched in the PubMed, Web of Science, Embase databases, Google Scholar, Yahoo and Baidu. Pooled weighed mean difference (WMD) or odds ratio (OR) with their 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. A total of nine articles with 8871 subjects were investigated in the present meta-analysis. Overall, the TT/TC genotypes of LCT 13910 C/T polymorphism showed significantly higher BMD than those with the CC genotype at femur neck (FN) (\(\hbox {WMD} = 0.011\,\hbox {g/cm}^{2}\), 95% CI \(=\) 0.004–0.018, \(P = 0.003\)). Besides, LCT 13910 C/T polymorphism may decrease the risk of any site fractures (for TT versus TC \(+\) CC, OR \(=\) 0.813, 95% CI \(=\) 0.704–0.938, \(P = 0.005\); for T allele versus C allele, OR \(=\) 0.885, 95% CI \(=\) 0.792–0.989, \(P = 0.032\)). However, there was no significant association of LCT 13910 C/T polymorphism with BMD at lumbar spine and risk of vertebral fractures under all genetic contrast models (all P values were \({>}0.05\)). The meta-analysis suggests that there are significant effects of LCT 13910 C/T polymorphism on BMD and fracture risk. Large-scale studies with different ethnic populations will be needed to further investigate the possible race-specific effect of LCT 13910 C/T polymorphism on BMD and fracture risk.
... A lactose-free diet has been associated with an increased risk of certain health conditions related to a low vitamin D intake (5). Moreover, the consumption of lactose-free beverages in preschool-aged children has been associated with a higher risk of suboptimal plasma 25hydroxyvitamin D [25(OH)D] (6), yet the association between LI and 25(OH)D plasma concentrations is not clear (5,7,8). ...
... In the presence of the T allele, the age-dependent DNA methylation is not significant, and it does not lead to lactase downregulation in adulthood (10). An association between the LCT-13910C>T genotype and differences in height has been reported previously (7,(41)(42)(43), and this appears to be driven by the influence of the LCT genotype on milk consumption. Daily milk consumption of 254 mL has been shown to contribute an annual increase of 0.4 cm in height (44). ...
Background: The LCT-13910C>T gene variant is associated with lactose intolerance (LI) in different ethnic groups. Individuals with LI often limit or avoid dairy consumption, a major dietary source of vitamin D in North America, which may lead to inadequate vitamin D intake.
Objective: The objective was to determine the prevalence of genotypes predictive of LI in different ethnic groups living in Canada and to determine whether the LCT genotype is associated with plasma 25(OH)D concentrations.
Methods: Blood samples were drawn from a total of 1495 men and women aged 20–29 y from the Toronto Nutrigenomics and Health Study for genotyping and plasma 25(OH)D analysis. Intakes of dairy were assessed by using a 196-item food frequency questionnaire. The prevalence of LCT-13910C>T genotypes was compared by using χ² analysis. Using a Mendelian randomization approach, we examined the association between LCT genotypes and 25(OH)D concentrations.
Results: Approximately 32% of Caucasians, 99% of East Asians, 74% of South Asians, and 59% of those with other or mixed ethnicities had the CC genotype associated with LI. Compared with those with the TT genotype, those with the CC genotype had a lower mean ± SE total dairy intake (2.15 ± 0.09 compared with 2.67 ± 0.12 servings/d, P = 0.003), a lower skim-milk intake (0.20 ± 0.03 compared with 0.46 ± 0.06 servings/d, P = 0.0004), and a lower plasma 25(OH)D concentration (63 ± 1.9 compared with 75.8 ± 2.4 nmol/L, P < 0.0001). The CT and CC genotypes were associated with a 50% and a 2-fold increased risk, respectively, of a suboptimal plasma 25(OH)D concentration (<75 nmol/L).
Conclusions: In Caucasians, the CC genotype that predicts LI is associated with a lower plasma 25(OH)D concentration, which is attributable at least in part to a lower intake of dairy, particularly skim milk. Increased risk of suboptimal concentrations of vitamin D was also observed among those with the CT genotype, suggesting an intermediate effect of the heterozygous genotype.
... As a result, a majority of AAs who do not carry the variant might limit their dairy food intake and, subsequently, vitamin D intake. In European populations, this SNP was associated with intake of dairy products and dietary calcium (46,47) but not strongly associated with serum 25(OH)D concentrations (47). Note that this SNP was not associated with 25(OH)D concentrations in previous GWASs in European populations (32,33). ...
... As a result, a majority of AAs who do not carry the variant might limit their dairy food intake and, subsequently, vitamin D intake. In European populations, this SNP was associated with intake of dairy products and dietary calcium (46,47) but not strongly associated with serum 25(OH)D concentrations (47). Note that this SNP was not associated with 25(OH)D concentrations in previous GWASs in European populations (32,33). ...
Background: Vitamin D may have anticancer activities. The high prevalence of vitamin D deficiency in African Americans (AAs) may be a contributing factor to the cancer health disparities between AAs and European Americans (EAs).
Objectives: We compared concentrations of 25(OH)D and vitamin D–binding protein (VDBP) in AA and EA women and investigated determinants of the vitamin D–biomarker concentrations in both populations.
Design: We used data and biospecimens from 909 AA and 847 EA healthy control subjects from the Carolina Breast Cancer Study (CBCS) and the Women’s Circle of Health Study (WCHS) in the African American Breast Cancer Epidemiology and Risk Consortium. We measured plasma 25(OH)D and VDBP concentrations in all participants and genotyped 67 vitamin D–related genes in AA women only.
Results: AA women had lower 25(OH)D concentrations than did EA women (mean ± SD: 14.2 ± 8.1 compared with 21.1 ± 11.5 ng/mL, respectively; P < 0.0001) but similar concentrations of VDBP (mean ± SD: 344 ± 133 compared with 336 ± 124 μg/mL, respectively; P = 0.25). With VDBP and other factors controlled for, the observed racial difference in 25(OH)D concentrations did not diminish. Relations of demographic and lifestyle factors with 25(OH)D were similar between AA and EA women. Although none of the genetic variants that have been identified in previous genome-wide association studies of 25(OH)D concentrations in EAs were significant (P > 0.05) in AAs, AA women who carried the allele of a functional single nucleotide polymorphism rs4988235, which has been previously associated with lactase expression and lactose tolerance, had higher dietary vitamin D intake and higher measured 25(OH)D concentrations.
Conclusions: AA women have lower concentrations of total 25(OH)D than EA women do, but both groups have similar VDBP concentrations, suggesting that there are lower concentrations of free 25(OH)D in AAs. Although demographic and lifestyle determinants of 25(OH)D concentrations are similar between the 2 groups, genetic determinants may be ethnicity specific. Larger studies in AAs will be needed to fully elucidate the underlying determinants of low vitamin D concentrations in AA populations.
