Genetic Polymorphism of Human Y Chromosome and Risk Factors for Cardiovascular Diseases: A Study in WOBASZ Cohort

<div><p>Genetic variants of Y chromosome predispose to hypertension in rodents, whereas in humans the evidence is conflicting. Our purpose was to study the distribution of a panel of Y chromosome markers in a cohort from a cross-sectional population-based study on the prevalence of cardiovascular risk factors in Poland (WOBASZ study). The HindIII, YAP Y chromosome variants, previously shown to influence blood pressure, lipid traits or height, as well as SNPs defining main Y chromosome haplogroups, were typed in 3026, 2783 and 2652 samples, respectively. In addition, 4 subgroups (N∼100 each) representing extremes of LDL concentration or blood pressure (BP) were typed for a panel of 17 STRs. The HindIII and YAP polymorphism were not associated with any of the studied traits. Analysis of the haplogroup distribution showed an association between higher HDL level and hg I-M170 (P = 0.02), higher LDL level and hg F*(xI-M170, J2-M172, K-M9) (P = 0.03) and lower BMI and hg N3-Tat (P = 0.04). Analysis of STRs did not show statistically significant differences. Since all these associations lost statistical significance after Bonferroni correction, we conclude that a major role of Y chromosome genetic variation (defined by HindIII, YAP or main Y chromosome haplogroups) in determining cardiovascular risk in Poles is unlikely.</p></div

Distribution of studied parameters according to Y chromosome HindIII and YAP markers.

<p>Distribution of studied parameters according to Y chromosome HindIII and YAP markers.</p

Distribution of studied parameters according to Y chromosome haplogroup (only haplogroups with n>10 were analyzed).

<p>TC –total cholesterol, M – Mean, SD standard deviation, P - p value (t-test vs. all other haplogroups), BP blood pressure, TG-triglycerides</p

Distribution of the <i>FLG</i> variants in subjects with atopic asthma (AA) stratified by diagnosis of atopic dermatitis.

<p>All comparisons vs. healthy controls (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016933#pone-0016933-t001" target="_blank">Table 1</a>), NA: not available.</p

Distribution of the <i>FLG</i> variants in subjects with persistent allergic rhinitis (pAR) stratified by diagnosis of atopic dermatitis.

<p>All comparisons vs. healthy controls (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016933#pone-0016933-t001" target="_blank">Table 1</a>), NA: not available.</p

Prevalence of the <i>FLG</i> variants vs. concordance between diagnosis of asthma (all kinds or atopic asthma) by a physician (i.e. diagnosed during the present study) and individual awareness of having asthma (all kinds) according to questionnaire data.

<p>* Calculated for the comparison of the frequency of the combined genotype (2282del4 or R501X) vs. healthy controls. Cells with P values <0.05 are <b>boldfaced</b>; Questionnaire data were not available in 18 subjects with asthma including 9 with AA.</p

Prevalence of <i>FLG</i> variants according to clinical diagnosis.

1<p>In 24 subjects allergic rhinitis could not be classified as intermittent or persistent; NA not applicable; All comparisons vs. healthy controls.</p

Haplotype dependent association of rs7927894 (11q13.5) with atopic dermatitis and chronic allergic rhinitis: A study in ECAP cohort

<div><p>The T allele of rs7927894 (at 11q13.5) was associated with atopic dermatitis and other allergic diseases. Our purpose was to replicate the association with allergic phenotypes and explore the role of rs7927894 in predisposing to persistent allergic rhinitis and atopic asthma. We also wanted to explore if other SNPs at 11q13.5 contributed to effect of rs7927894. We studied patients with atopic dermatitis (N = 270), atopic asthma (N = 486), persistent allergic rhinitis (N = 589) and controls matched for age, sex and region (N = 540, N = 372 and N = 1178, respectively). We found that rs7927894 T was associated with atopic dermatitis (OR = 1.39, CI: 1.12–1.73, P = 0.003) and independently with persistent allergic rhinitis (OR = 1.24, CI:1.07–1.43, P = 0.0043, P_corrected = 0.013) but not atopic asthma. Analysis of additional tagging SNPs (rs7930763, rs2513517, rs7125552) showed that effect of rs7927894 T was limited to haplotypes encoding G at rs7125552. In conclusion, rs7927894 T is associated not only with atopic dermatitis but also persistent allergic rhinitis. Since these effects are haplotype dependent rs7927894 alone does not account for the association between 11q13.5 and atopic dermatitis/persistent allergic rhinitis.</p></div

Distribution of alleles and genotypes of rs7927894 among patients and controls.

<p>Distribution of alleles and genotypes of rs7927894 among patients and controls.</p

Distribution of genotypes of 11q13.5 SNPs among subjects with AD and controls.

<p>Distribution of genotypes of 11q13.5 SNPs among subjects with AD and controls.</p