Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians
| العنوان: | Assessment of established HDL-C loci for association with HDL-C levels and type 2 diabetes in Pima Indians |
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| المؤلفون: | Clifton Bogardus, Manmeet Kaur, William C. Knowler, Sayuko Kobes, Paolo Piaggi, Nellie A. McLean, Leslie J. Baier, Robert L. Hanson, Anup K. Nair |
| المصدر: | Diabetologia. 59:481-491 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, KLF14, Type 2 diabetes, HDL/*blood/genetics Diabetes Mellitus, Type 2/*blood/genetics Female Genetic Predisposition to Disease/genetics Hepatocyte Nuclear Factor 4/genetics Humans Indians, Epidemiology, Child, Aged, 80 and over, Sp Transcription Factors, Genetics, biology, North American/genetics Male Middle Aged Polymorphism, Middle Aged, Hepatocyte Nuclear Factor 4, Female, lipids (amino acids, peptides, and proteins), Adult, medicine.medical_specialty, Diabetes risk, Adolescent, Kruppel-Like Transcription Factors, Locus (genetics), Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Article, Young Adult, 03 medical and health sciences, Sex Factors, Internal medicine, Cholesterylester transfer protein, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Allele, Aged, business.industry, Cholesterol, HDL, nutritional and metabolic diseases, Adolescent Adult Aged Aged, 80 and over Child Cholesterol Ester Transfer Proteins/genetics Cholesterol, HDL/*blood/genetics Diabetes Mellitus, Type 2/*blood/genetics Female Genetic Predisposition to Disease/genetics Hepatocyte Nuclear Factor 4/genetics Humans Indians, North American/genetics Male Middle Aged Polymorphism, Single Nucleotide/genetics Sex Factors Sp Transcription Factors/genetics Young Adult Cetp Hdl-c Hnf4a Klf14 Lipids Pima Indians Type 2 diabetes, medicine.disease, Cholesterol Ester Transfer Proteins, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, Indians, North American, Single Nucleotide/genetics Sex Factors Sp Transcription Factors/genetics Young Adult Cetp Hdl-c Hnf4a Klf14 Lipids Pima Indians Type 2 diabetes, biology.protein, 80 and over Child Cholesterol Ester Transfer Proteins/genetics Cholesterol, business, Adolescent Adult Aged Aged |
| الوصف: | Epidemiological studies in Pima Indians identified elevated levels of HDL-cholesterol (HDL-C) as a protective factor against type 2 diabetes risk in women. We assessed whether HDL-C-associated single-nucleotide polymorphisms (SNPs) also associate with type 2 diabetes in female Pima Indians.Twenty-one SNPs in established HDL-C loci were initially analysed in 2,675 full-heritage Pima Indians. SNPs shown to associate with HDL-C (12 SNPs) were assessed for association with type 2 diabetes in 7,710 Pima Indians (55.6% female sex). The CETP locus provided the strongest evidence for association with HDL-C and was further interrogated by analysing tag SNPs.Twelve of the 21 SNPs analysed had a significant association with HDL-C in Pima Indians; five SNPs representing four loci (CETP, DOCK6, PPP1R3B and ABCA1) reached genome-wide significance. Three SNPs, at CETP, KLF14 and HNF4A, associated with type 2 diabetes only in female participants with the HDL-C-lowering allele increasing diabetes risk (p values: 3.2 × 10(-4) to 7.7 × 10(-5)); the association remained significant even after adjustment for HDL-C. Additional analysis across CETP identified rs6499863 as having the strongest association with type 2 diabetes in female participants (p = 5.0 × 10(-6)) and this association remained independent of the HDL-C association.SNPs at the CETP, HNF4A and KLF14 locus are associated with HDL-C levels and type 2 diabetes (in female participants). However, since HNF4A and KLF14 are established loci for type 2 diabetes, it is unlikely that HDL-C solely mediates these associations. |
| تدمد: | 1432-0428 0012-186X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ad4f2c53f3b3b595f1c590b22cf44dbTest https://doi.org/10.1007/s00125-015-3835-xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4ad4f2c53f3b3b595f1c590b22cf44db |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320428 0012186X |
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