HindIII(+/-) polymorphism of the Y chromosome, blood pressure, and serum lipids: no evidence of association in three white populations.
BACKGROUND
Male sex is associated with elevated levels of cardiovascular risk factors, including higher blood pressure (BP). Genetic variants on the Y chromosome may contribute to explain the sexual dimorphism in cardiovascular diseases. Among them, the HindIII(+/-) polymorphism of the male-specific region of the Y chromosome has been associated with BP and serum cholesterol levels, with conflicting results. We evaluated the association between the HindIII(+/-) polymorphism, prevalence of hypertension, BP, and serum lipid levels in a large sample of white men and the previously reported epistatic interaction between HindIII(+/-) and the -344C/T polymorphism of the aldosterone synthase gene (CYP11B2) on BP.


METHODS
From three European populations (UK n = 422; Belgium n = 313; Italy n = 1248) 1983 white men were phenotyped for BP and serum lipids and genotyped for HindIII(+/-) site and for -344C/T polymorphism in the promoter of CYP11B2 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).


RESULTS
A higher frequency of the HindIII (+) was found in Italians (63%) as compared to both British (31%) and Belgians (28%) (P < .0001). We found no evidence of association of the HindIII(+/-) site with prevalence of hypertension, BP, and serum lipids in any of the three European populations examined and in the entire sample. Finally, we did not observe any interaction between the HindIII(+/-) polymorphism and the -344C/T variant of CYP11B2 on BP.


CONCLUSIONS
Our data do not support the hypothesis that the HindIII(+/-) site of the Y chromosome is a marker of cardiovascular risk in white men, highlighting the need for replication in genetic association studies.
Unit of Epidemiology & Population Genetics, Institute of Food Sciences, CNR, Avellino, Italy.
Paola
P
Russo
Antonella
A
Venezia
Fabio
F
Lauria
Pasquale
P
Strazzullo
Francesco P
FP
Cappuccio
Licia
L
Iacoviello
Gianvincenzo
G
Barba
Alfonso
A
Siani
D000328:Adult; D001794:Blood Pressure / Q000235:genetics* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D041322:Chromosomes, Human, Y / Q000235:genetics*; D003430:Cross-Sectional Studies; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000502:physiology; D005060:Europe; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D012307:Risk Factors; D012727:Sex Characteristics; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics* / Q000502:physiology; D044465:White People / Q000235:genetics*
D005819:Genetic Markers; D008055:Lipids; D002784:Cholesterol; D019405:Cytochrome P-450 CYP11B2; C090528:DNA modification methylase HindIII; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)