Haptoglobin 2-2 genotype is not associated with cardiovascular risk in subjects with elevated glycohemoglobin-results from the Bruneck Study.
BACKGROUND
Haptoglobin (Hp) is an abundant plasma protein with antioxidant properties. The Hp 2-2 genotype has previously been linked to coronary heart disease risk in individuals with elevated glycosylated hemoglobin (HbA1c). We investigated the association of Hp and HbA1c with cardiovascular disease (CVD) in the longitudinal, population-based Bruneck Study.


RESULTS
Hp genotype was determined by polymerase chain reaction according to standard procedures and HbA1c concentration by a Diabetes Control and Complications Trial-aligned assay. HbA1c was measured in 1995, 2000, and 2005. Occurrence of the combined CVD endpoint of myocardial infarction or stroke was recorded between 1995 and 2010. Outcome analyses employed the Cox proportional hazards model with HbA1c category as time-varying covariate. At baseline in 1995, 806 subjects (male sex, 49.3%; age, mean ± standard deviation, 62.70 ± 11.08 years) were included. During follow-up, 123 subjects experienced at least 1 CVD event (48 suffered myocardial infarction, 68 stroke, and 7 both). Among subjects with HbA1c ≥ 6.5% (≥ 48 mmol/mol), those with the Hp 2-2 genotype did not show an elevated risk of incident CVD compared with those with other genotypes (age- and sex-adjusted hazard ratio [95% CI], 0.47 [0.19, 1.13], P=0.092) and a null association was also observed in subjects with HbA1c<6.5% (1.10 [0.75, 1.62], P=0.629) (P for interaction=0.082).


CONCLUSIONS
Subjects with the Hp 2-2 genotype and elevated HbA1c compared with subjects with other Hp genotypes and elevated HbA1c did not show increased CVD risk.
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (R.P., S.K., P.W., J.W.).
Raimund
R
Pechlaner
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (R.P., S.K., P.W., J.W.).
Stefan
S
Kiechl
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (R.P., S.K., P.W., J.W.) Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (P.W.).
Peter
P
Willeit
Department of Internal Medicine VI, Medical University Innsbruck, Innsbruck, Austria (E.D., W.).
Egon
E
Demetz
Division of Genetic Epidemiology, Medical University Innsbruck, Innsbruck, Austria (M.H., F.K.).
Margot
M
Haun
Department of Internal Medicine, Hospital of Bruneck, Bruneck, Italy (S.W., F.O.).
Siegfried
S
Weger
Department of Internal Medicine, Hospital of Bruneck, Bruneck, Italy (S.W., F.O.).
Friedrich
F
Oberhollenzer
Division of Genetic Epidemiology, Medical University Innsbruck, Innsbruck, Austria (M.H., F.K.).
Florian
F
Kronenberg
Division of Endocrinology, Diabetes and Metabolic Diseases, University and Hospital Trust of Verona, Verona, Italy (E.B.).
Enzo
E
Bonora
Department of Internal Medicine VI, Medical University Innsbruck, Innsbruck, Austria (E.D., W.).
Günter
G
Weiss
Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (R.P., S.K., P.W., J.W.).
Johann
J
Willeit
D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis*; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000235:genetics
D006442:Glycated Hemoglobin; D006242:Haptoglobins; C517652:hemoglobin A1c protein, human
cardiovascular diseases; diabetes mellitus; genetics