Association of rs2000999 in the haptoglobin gene with total cholesterol, HDL-C, and LDL-C levels in Mexican type 2 diabetes patients

Abstract Recently, studies have shown significant association between the rs2000999 polymorphism in the haptoglobin-encoding gene (HP) and low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, which are important risk factors for cardiovascular diseases. However, the association of rs2000999 with serum lipids in Latin American diabetic populations is still uncharacterized. Here, we analyzed the association of rs2000999 with TC, high-density lipoprotein cholesterol (HDL-C), and LDL-C levels in 546 Mexican adults with type 2 diabetes (T2D) and in 654 controls without T2D. In this observational case-control study we included adults from 4 centers of the Mexican Social Security Institute in Mexico City recruited from 2012 to 2015. TC, HDL-C, LDL-C, triglycerides (TG), and glucose levels were measured by an enzymatic colorimetric method. The variant rs2000999 was genotyped using TaqMan real time polymerase chain reaction. The percentage of Native-American ancestry showed a negative association with the rs2000999 A allele. In contrast, the rs2000999 A allele had a strong positive association with European ancestry, and to a lesser extent, with African ancestry. Linear regression was used to estimate the association between the variant rs2000999 and lipid concentrations, using different genetic models. Under codominant and recessive models, rs2000999 was significantly associated with TC and LDL-C levels in the T2D group and in controls without T2D. In addition, the group with T2D showed a significant association between the variant and HDL-C levels. In summary, the rs2000999 A allele in Mexican population is positively associated with the percentage of European and negatively associated with Native American ancestry. Carriers of the A allele have increased levels of TC and LDL-C, independently of T2D diagnosis, and also increased concentrations of HDL-C in the T2D sample.

[1]  Tom R. Gaunt,et al.  Genetic determinants of circulating haptoglobin concentration , 2019, Clinica chimica acta; international journal of clinical chemistry.

[2]  Cheng Hu,et al.  Association of the genetic variant rs2000999 with haptoglobin and diabetic macrovascular diseases in Chinese patients with type 2 diabetes. , 2019, Journal of diabetes and its complications.

[3]  Nicholette D. Palmer,et al.  Genetic architecture of lipid traits in the Hispanic community health study/study of Latinos , 2017, Lipids in Health and Disease.

[4]  J. Denny,et al.  A common deletion in the haptoglobin gene associated with blood cholesterol levels among Chinese women , 2017, Journal of Human Genetics.

[5]  D. Vigerust,et al.  Role of Haptoglobin in Health and Disease: A Focus on Diabetes , 2016, Clinical Diabetes.

[6]  R. Handsaker,et al.  Recurring exon deletions in the haptoglobin ( HP ) gene associate with lower blood cholesterol levels , 2016 .

[7]  Jason M. Torres,et al.  Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs , 2016, Scientific Reports.

[8]  Fengtang Yang,et al.  Haptoglobin (HP) and Haptoglobin-related protein (HPR) copy number variation, natural selection, and trypanosomiasis , 2013, Human Genetics.

[9]  P. Elliott,et al.  A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels , 2012, PloS one.

[10]  V. Basevi,et al.  Standards of Medical Care in Diabetes—2012 , 2011, Diabetes Care.

[11]  C. Barbatis,et al.  Association of haptoglobin genotype and common cardiovascular risk factors with the amount of iron in atherosclerotic carotid plaques. , 2011, Atherosclerosis.

[12]  S. Moestrup,et al.  Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging. , 2009, Blood.

[13]  L. Cigliano,et al.  Haptoglobin binds apolipoprotein E and influences cholesterol esterification in the cerebrospinal Fluid , 2009, Journal of neurochemistry.

[14]  K. Tadokoro,et al.  Detection of Hpdel among Thais, a deleted allele of the haptoglobin gene that causes congenital haptoglobin deficiency , 2007, Transfusion.

[15]  H. Coon,et al.  BMC Genetics BioMed Central , 2007 .

[16]  M. Worwood,et al.  Haptoglobin: a review of the major allele frequencies worldwide and their association with diseases , 2007, International journal of laboratory hematology.

[17]  Fernando Costa,et al.  Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. , 2005, Circulation.

[18]  K. U. Park,et al.  Haptoglobin genotypic distribution (including Hp0 allele) and associated serum haptoglobin concentrations in Koreans , 2004, Journal of Clinical Pathology.

[19]  K. Jablonski,et al.  Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. , 2002, Journal of the American College of Cardiology.

[20]  L. Cigliano,et al.  Haptoglobin inhibits lecithin‐cholesterol acyltransferase in human ovarian follicular fluid , 2001, Molecular reproduction and development.

[21]  I. Hochberg,et al.  Haptoglobin phenotype and vascular complications in patients with diabetes. , 2000, The New England journal of medicine.

[22]  J. Carpenter,et al.  Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African‐American populations , 2000, Annals of human genetics.

[23]  G. De Backer,et al.  Associations between haptoglobin polymorphism, lipids, lipoproteins and inflammatory variables. , 1999, Atherosclerosis.

[24]  Szu-Chin Li,et al.  Detection of Hpdel in healthy individuals and cancer patients in Taiwan , 2009, Clinical chemistry and laboratory medicine.

[25]  M. Sonati,et al.  Polymorphism of human haptoglobin and its clinical importance , 2008 .