Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population
Abstract Background The goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population. Methods Three tag single nucleotide polymorphisms (SNPs) (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan a...
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BMC
2018-08-01
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| Series: | Lipids in Health and Disease |
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| Online Access: | http://link.springer.com/article/10.1186/s12944-018-0819-0 |
| _version_ | 1818026391325638656 |
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| author | Jian Jia Yayu Tang Chong Shen Ning Zhang Haixia Ding Yiyang Zhan |
| author_facet | Jian Jia Yayu Tang Chong Shen Ning Zhang Haixia Ding Yiyang Zhan |
| author_sort | Jian Jia |
| collection | DOAJ |
| description | Abstract Background The goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population. Methods Three tag single nucleotide polymorphisms (SNPs) (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan assays to determine VDR SNP associations with dyslipidemia. We genotyped 877 cases of dyslipidemia from a normotensive, non-diabetes mellitus population and 1822 non-dyslipidemia subjects in a stage I study. In a follow-up stage II study, we included a larger sample of 3124 controls and 1679 cases with dyslipidemia. Finally, we explored the potential molecular mechanism for the SNP associations using molecular modeling analysis. Results We found a significant association between SNP rs2228570 and dyslipidemia in the additive (adjusted odds ratio (OR) = 1.255, 95% Confidence Interval (CI) = (1.118–1.409), P < 0.001), dominant (OR = 1.384, 95% CI = 1.384 (1.136–1.6), P = 0.001) and recessive models (OR = 1.356, 95%CI = 1.1–1.671, P = 0.004) in stage I. We further established that the rs2228570 variant was significantly associated with dyslipidemia in the additive (adjusted OR = 1.146, 95% CI = 1.053–1247, P = 0.002), dominant (OR = 1.184, 95%CI =1.018–1.376, P = 0.028) and recessive models (OR = 1.209, 95%CI = 1.064–1.374, P = 0.004) in stage II. The TT genotype was significantly higher (4.93 ± 0.75 mmol/L) compared to the TC (4.67 ± 0.47 mmol/L) or CC (4.66 ± 0.44 mmol/L) genotype (P = 0.01) in cases with elevated low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the cases with the TT genotype had significantly lower serum 25(OH)D levels (18.43 ± 5.04 ng/ mL) compared to the TC (26.24 ± 4.16 ng/mL) and CC (36.76 ± 8.10 ng/ mL) genotypes (P < 0.001). Multivariable linear regression analysis indicated that the rs2228750 genotype significantly correlated with serum low-density lipoprotein-C (LDL-C) levels in cases with dyslipidemia. Using molecular modeling analysis, we further found that the rs2228570 variant changed the structure and the stability of VDR and altered the binding energy of its ligand. Conclusions The VDR rs2228570 variant may increase susceptibility to dyslipidemia in the Chinese Han population. |
| first_indexed | 2024-12-10T04:31:15Z |
| format | Article |
| id | doaj.art-6d291532d5204ec194362cd8b30cefb1 |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-12-10T04:31:15Z |
| publishDate | 2018-08-01 |
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| series | Lipids in Health and Disease |
| spelling | doaj.art-6d291532d5204ec194362cd8b30cefb12022-12-22T02:02:09ZengBMCLipids in Health and Disease1476-511X2018-08-011711810.1186/s12944-018-0819-0Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han populationJian Jia0Yayu Tang1Chong Shen2Ning Zhang3Haixia Ding4Yiyang Zhan5General Internal Medicine Department, The First Affiliated Hospital of Nanjing Medical UniversityGeriatric Medicine Department, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical UniversityGeriatric Medicine Department, The First Affiliated Hospital of Nanjing Medical UniversityGeriatric Medicine Department, The First Affiliated Hospital of Nanjing Medical UniversityGeriatric Medicine Department, The First Affiliated Hospital of Nanjing Medical UniversityAbstract Background The goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population. Methods Three tag single nucleotide polymorphisms (SNPs) (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan assays to determine VDR SNP associations with dyslipidemia. We genotyped 877 cases of dyslipidemia from a normotensive, non-diabetes mellitus population and 1822 non-dyslipidemia subjects in a stage I study. In a follow-up stage II study, we included a larger sample of 3124 controls and 1679 cases with dyslipidemia. Finally, we explored the potential molecular mechanism for the SNP associations using molecular modeling analysis. Results We found a significant association between SNP rs2228570 and dyslipidemia in the additive (adjusted odds ratio (OR) = 1.255, 95% Confidence Interval (CI) = (1.118–1.409), P < 0.001), dominant (OR = 1.384, 95% CI = 1.384 (1.136–1.6), P = 0.001) and recessive models (OR = 1.356, 95%CI = 1.1–1.671, P = 0.004) in stage I. We further established that the rs2228570 variant was significantly associated with dyslipidemia in the additive (adjusted OR = 1.146, 95% CI = 1.053–1247, P = 0.002), dominant (OR = 1.184, 95%CI =1.018–1.376, P = 0.028) and recessive models (OR = 1.209, 95%CI = 1.064–1.374, P = 0.004) in stage II. The TT genotype was significantly higher (4.93 ± 0.75 mmol/L) compared to the TC (4.67 ± 0.47 mmol/L) or CC (4.66 ± 0.44 mmol/L) genotype (P = 0.01) in cases with elevated low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the cases with the TT genotype had significantly lower serum 25(OH)D levels (18.43 ± 5.04 ng/ mL) compared to the TC (26.24 ± 4.16 ng/mL) and CC (36.76 ± 8.10 ng/ mL) genotypes (P < 0.001). Multivariable linear regression analysis indicated that the rs2228750 genotype significantly correlated with serum low-density lipoprotein-C (LDL-C) levels in cases with dyslipidemia. Using molecular modeling analysis, we further found that the rs2228570 variant changed the structure and the stability of VDR and altered the binding energy of its ligand. Conclusions The VDR rs2228570 variant may increase susceptibility to dyslipidemia in the Chinese Han population.http://link.springer.com/article/10.1186/s12944-018-0819-0Vitamin D receptorPolymorphismDyslipidemiaChinese |
| spellingShingle | Jian Jia Yayu Tang Chong Shen Ning Zhang Haixia Ding Yiyang Zhan Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population Lipids in Health and Disease Vitamin D receptor Polymorphism Dyslipidemia Chinese |
| title | Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population |
| title_full | Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population |
| title_fullStr | Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population |
| title_full_unstemmed | Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population |
| title_short | Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population |
| title_sort | vitamin d receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum ldl levels in chinese han population |
| topic | Vitamin D receptor Polymorphism Dyslipidemia Chinese |
| url | http://link.springer.com/article/10.1186/s12944-018-0819-0 |
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