Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients
Abstract Background Haptoglobin (Hp) functions as an antioxidant by binding with haemoglobin. We investigated whether serum Hp has a causal effect on macroangiopathy via Mendelian randomization (MR) analysis with common variants of the Hp gene in Chinese patients with type 2 diabetes. Methods A tota...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12933-018-0662-7 |
| _version_ | 1818201464901730304 |
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| author | Shiyun Wang Jie Wang Rong Zhang Tao Wang Dandan Yan Zhen He Feng Jiang Cheng Hu Weiping Jia |
| author_facet | Shiyun Wang Jie Wang Rong Zhang Tao Wang Dandan Yan Zhen He Feng Jiang Cheng Hu Weiping Jia |
| author_sort | Shiyun Wang |
| collection | DOAJ |
| description | Abstract Background Haptoglobin (Hp) functions as an antioxidant by binding with haemoglobin. We investigated whether serum Hp has a causal effect on macroangiopathy via Mendelian randomization (MR) analysis with common variants of the Hp gene in Chinese patients with type 2 diabetes. Methods A total of 5687 type 2 diabetes patients were recruited and genotyped for the Hp gene. Clinical features and vascular imaging tests were applied to diagnose macroangiopathy. The association between common Hp genotypes and macroangiopathy was analyzed in the whole population. Serum Hp levels were measured by enzyme-linked immunosorbent assay in a subset of 935 patients. We individually analyzed the correlations among Hp levels, Hp genotypes and macroangiopathy. Further, 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative marker of DNA damage, was examined to evaluate the levels of oxidative stress. Results Common Hp genotypes were correlated with macroangiopathy (OR = 1.140 [95% CI 1.005–1.293], P = 0.0410 for the Hp 1 allele). Serum Hp levels were associated with both common Hp genotypes (P = 3.55 × 10−31) and macroangiopathy (OR = 2.123 [95% CI 1.098–4.102], P = 0.0252) in the subset of 935 patients. In the MR analysis, the directional trends of the observed and predicted relationships between common Hp genotypes and macroangiopathy were the same (OR 1.357 and 1.130, respectively). Furthermore, common Hp genotypes and Hp levels were associated with serum 8-OHdG levels (P = 0.0001 and 0.0084, respectively). Conclusions Our study provides evidence for a causal relationship between serum Hp levels and macroangiopathy in Chinese type 2 diabetes patients by MR analysis. |
| first_indexed | 2024-12-12T02:53:59Z |
| format | Article |
| id | doaj.art-d5e174bd42a549da9393a398e713fbfb |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-12T02:53:59Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-d5e174bd42a549da9393a398e713fbfb2022-12-22T00:40:49ZengBMCCardiovascular Diabetology1475-28402018-01-0117111110.1186/s12933-018-0662-7Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patientsShiyun Wang0Jie Wang1Rong Zhang2Tao Wang3Dandan Yan4Zhen He5Feng Jiang6Cheng Hu7Weiping Jia8Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalAbstract Background Haptoglobin (Hp) functions as an antioxidant by binding with haemoglobin. We investigated whether serum Hp has a causal effect on macroangiopathy via Mendelian randomization (MR) analysis with common variants of the Hp gene in Chinese patients with type 2 diabetes. Methods A total of 5687 type 2 diabetes patients were recruited and genotyped for the Hp gene. Clinical features and vascular imaging tests were applied to diagnose macroangiopathy. The association between common Hp genotypes and macroangiopathy was analyzed in the whole population. Serum Hp levels were measured by enzyme-linked immunosorbent assay in a subset of 935 patients. We individually analyzed the correlations among Hp levels, Hp genotypes and macroangiopathy. Further, 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative marker of DNA damage, was examined to evaluate the levels of oxidative stress. Results Common Hp genotypes were correlated with macroangiopathy (OR = 1.140 [95% CI 1.005–1.293], P = 0.0410 for the Hp 1 allele). Serum Hp levels were associated with both common Hp genotypes (P = 3.55 × 10−31) and macroangiopathy (OR = 2.123 [95% CI 1.098–4.102], P = 0.0252) in the subset of 935 patients. In the MR analysis, the directional trends of the observed and predicted relationships between common Hp genotypes and macroangiopathy were the same (OR 1.357 and 1.130, respectively). Furthermore, common Hp genotypes and Hp levels were associated with serum 8-OHdG levels (P = 0.0001 and 0.0084, respectively). Conclusions Our study provides evidence for a causal relationship between serum Hp levels and macroangiopathy in Chinese type 2 diabetes patients by MR analysis.http://link.springer.com/article/10.1186/s12933-018-0662-7HaptoglobinMendelian randomizationMacroangiopathyType 2 diabetes |
| spellingShingle | Shiyun Wang Jie Wang Rong Zhang Tao Wang Dandan Yan Zhen He Feng Jiang Cheng Hu Weiping Jia Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients Cardiovascular Diabetology Haptoglobin Mendelian randomization Macroangiopathy Type 2 diabetes |
| title | Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients |
| title_full | Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients |
| title_fullStr | Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients |
| title_full_unstemmed | Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients |
| title_short | Mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in Chinese type 2 diabetes patients |
| title_sort | mendelian randomization analysis to assess a causal effect of haptoglobin on macroangiopathy in chinese type 2 diabetes patients |
| topic | Haptoglobin Mendelian randomization Macroangiopathy Type 2 diabetes |
| url | http://link.springer.com/article/10.1186/s12933-018-0662-7 |
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