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Periodontal disease (PD) shares common risk factors with cardiovascular disease. Our hypothesis was that having a family history of myocardial infarction (FamHxMI) may be a novel risk factor for PD. Risk assessment based on FamHxMI, conditional on smoking status, was examined given the strong influence of smoking on PD. Exploratory analysis with inflammatory biomarkers and genetic determinants was conducted to understand potential mechanistic links. The Women's Genome Health Study (WGHS) is a prospective cohort of US female health care professionals who provided blood samples at baseline in the Women's Health Study, a 2 × 2 factorial clinical trial investigating vitamin E and aspirin in the prevention of cardiovascular disease and cancer. PD was ascertained via self-report over 12 y of follow-up. Prevalence (3,442 cases), incidence (1,365 cases), and survival analysis of PD were investigated for associations of FamHxMI as well as in strata of FamHxMI by smoking. Kruskal-Wallis, chi-square tests, multivariate regression, and Cox proportional hazard models were used for the analyses. In the WGHS, women with FamHxMI showed higher risk of ever having PD. A particularly high-risk group of having both FamHxMI and smoking at baseline was highlighted in the prevalence and risk of developing PD. PD risk increased according to the following strata: no FamHxMI and nonsmokers (reference), FamHxMI and nonsmokers (hazard ratio [HR] = 1.2, 95% CI = 1.0 to 1.5), smokers without FamHxMI (HR = 1.3, 95% CI = 1.2 to 1.5), and smokers with FamHxMI (HR = 1.5, 95% CI = 1.2 to 1.8). An independent analysis by the dental Atherosclerosis Risk in Communities study ( N = 5,552) identified more severe periodontitis cases among participants in the high-risk group (smokers with FamHxMI). Further examination of interactions among inflammatory biomarkers or genetic exploration with FamHxMI did not explain the risk increase of PD associated with FamHxMI in the WGHS. Future efforts based on an integrative-omics approach may facilitate validation of these findings and suggest a mechanistic link between PD and FamHxMI. [ABSTRACT FROM AUTHOR]

Simple sequence length polymorphisms (SSLPs) are a widely used tool for genetic studies in humans and model animals. Experimental crosses among closely related strains that differ primarily in the trait that is to be mapped carry the advantage of avoiding co-segregation of potentially confounding traits. However, their realization is encumbered by the limited availability of newly arisen informative SSLPs among such strains. Here we report the establishment of a genome-wide SSLP panel for the spontaneously hypertensive rat (SHR) and its close relative, the stroke-prone SHR (SHRSP), consisting of a total of 273 polymorphic markers that were found among 2,734 rat SSLPs screened. In addition to limitations in numbers, we also found the distribution of informative markers to be heterogeneous, with clustering and paucity of informative markers, respectively, in particular regions. Notably, the majority of regions thus identified was also seen when we examined an unrelated set of strains from the literature, indicating, on a more generic level, the presence of mutagenically more and less stable genomic regions. Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: Telomere shortening has been implicated in neurodegenerative disorders. However, available data on the association between telomere length and Parkinson's disease (PD) are inconclusive., Methods: A nested case-control design was used amongst men participating in the prospective Physicians' Health Study. A large proportion of participants provided blood samples in 1997 and they were followed through 2010. Men with self-reported PD were age-matched to controls in a 1:2 ratio. Quantitative PCR was used to determine the telomere repeat copy number to single gene copy number ratio (TSR) in genomic DNA extracted from peripheral blood leukocytes. TSR was used as a measure for relative telomere length (RTL) in our analyses. Conditional logistic regression was used to determine the risk of PD associated with RTL., Results: Data on RTL were available from 408 cases and 809 controls. Median TSR was shorter in controls than in cases (47.7 vs. 50.2; P = 0.02). The age-adjusted odds ratio (OR) for PD was 0.66 [95% confidence interval (CI) 0.46-0.95; Ptrend over quartiles 0.02] comparing the lowest to the highest quartile. The pattern of association was unchanged when comparing RTL below versus above the median (age-adjusted OR 0.75; 95% CI 0.59-0.96). Associations were similar after additional adjustment for many covariates., Conclusion: Contrary to what was expected, in this large nested case-control study amongst men shorter telomeres were associated with reduced PD risk. Future research on the nature of this counterintuitive association is warranted., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

Data on the association of the MTHFR 677C→T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype-migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 ≥ weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 ≥ weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA.

Objective: Few studies have examined the association between genetic variants of the estrogen receptor beta (ESR2) and obesity in postmenopausal women., Methods: The relationship of three polymorphisms (rs1271572, rs1256049 and rs4986938) and their associated haplotypes in the ESR2 gene with obesity and overweight were evaluated in 561 apparently healthy women (median age 63 years) from the Women's Health Study. Most of the women were postmenopausal (99.1%). The associations between genotypes and haplotypes with obesity (BMI> or =30kg/m(2)) and overweight (BMI> or =25kg/m(2)) were evaluated by logistic regression, assuming an additive model., Results: No association was observed for any of the three polymorphisms with BMI, overweight or obesity. In haplotype analyses, one haplotype (major allele for all polymorphisms) was associated with a borderline inverse association with overweight but not obesity (OR=0.62, 95% CI=0.39-0.98)., Conclusions: An inverse and borderline significant association was found between the ESR2 G-G-G haplotype and overweight in postmenopausal women. Further investigation regarding the association between ESR2 and adiposity should be performed to confirm these findings.

Background: Interrelationships among the ACE deletion/insertion (D/I) polymorphism (rs1799752), migraine, and cardiovascular disease (CVD) are biologically plausible but remain controversial., Methods: Association study among 25,000 white US women, participating in the Women's Health Study, with information on the ACE D/I polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationship among genotype, migraine, and incident CVD., Results: At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During 11.9 years of follow-up, 625 CVD events occurred. We did not find an association of the ACE D/I polymorphism with migraine or migraine aura status. There was a lack of association between the ACE D/I polymorphism and incident major CVD, ischemic stroke, and myocardial infarction. Migraine with aura doubled the risk for CVD, but only for carriers of the DD (multivariable-adjusted relative risk [RR] = 2.10; 95% CI = 1.22-3.59; p = 0.007) and DI genotype (multivariable-adjusted RR = 2.31; 95% CI = 1.52-3.51; p < 0.0001). The risk was not significant among carriers of the II genotype, a pattern we observed for myocardial infarction and ischemic stroke., Conclusions: Data from this large cohort of women do not suggest an association of the ACE deletion/insertion (D/I) polymorphism with migraine, migraine aura status, or cardiovascular disease (CVD). The increased risk for CVD among migraineurs with aura was only apparent for carriers of the DD/DI genotype. Due to limited number of outcome events, however, future studies are warranted to further investigate this association.

Background: Variants in the advanced glycosylation end product-specific receptor (AGER) gene have been associated with diabetic vasculopathy, however their role in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM) are uncertain. We investigated the relationship of 3 polymorphisms (rs1800625, rs1800624 and rs2070600) in the AGER gene and their haplotypes with T2DM as well as insulin resistance., Methods: A case-control study from community-based population sample of the Boston metropolitan area was performed in 637 diabetic patients and 596 controls (non-diabetic). The relationships between genotypes and T2DM were evaluated by linear and logistic regression models. Associations with insulin resistance [using corrected insulin response (CIR-30), insulin sensitivity index (ISI-120) and oral glucose tolerance test] were also examined among controls., Results: We found no consistent association between prevalent type 2 diabetes mellitus, and "insulin indices" (CIR-30, ISI-120 and oral glucose tolerance test) and the AGER polymorphisms. The A allele in the rs1800624 was modestly associated with a progressive decrease in CIR-30 levels only among Black controls (p=0.03)., Conclusions: A suggestive association between the A allele in the rs1800624 and CIR-30 levels was found. Further large and multiethnic studies should be performed to clarify these relationships.

Plasma lipid metabolic and transfer processes have recently been suggested to play an important role in the development of early restenosis, a major complication of percutaneous transluminal coronary angioplasty (PTCA); in particular, the common variants of genes for cholesteryl ester transfer protein (CETP) and paraoxonase (PONA) have been implicated. We had the opportunity to investigate this question in a large, prospective cohort characterized by quantitative coronary angiography in all subjects. The CETP-TaqIB (intron 1), CETP-MspI (intron 8), and PONA-AlwI (exon 2) polymorphisms were characterized in a cohort of 779 patients of whom 342 ("cases") had developed restenosis (as defined by > 50% loss of lumen compared with immediate postprocedure results) at repeat angiography at 6 months post PTCA. Selected frequencies for CETP B1 and B2 alleles (absence/presence of TaqIB site) were 0.65 and 0.35 (cases) and 0.65 and 0.35 (controls), respectively; frequencies for CETP M1 and M2 alleles (absence/presence of MspI site) were 0.20 and 0.80 (cases), 0.21 and 0.79 (controls), respectively; frequencies for PONA A and B alleles (absence/presence of AlwI site) were 0.73 and 0.27 (cases), 0.72 and 0.28 (controls), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for gene-gene interaction, or an association between genotype and restenosis or degree of lumen loss (adjusted for covariates). Our data, collected in the largest study of its kind so far, indicate that the common variants for CETP and PONA are not associated with incidence of restenosis after PTCA, and are therefore not useful markers for risk assessment.

The D/I (deletion, D, insertion, I) polymorphism of the angiotensin-converting enzyme (ACE) gene has been extensively studied for its association with a number of cardiovascular and other disease states. However, its potential association with differential clinical efficacy of ACE inhibitors (ACE-I) administered to patients who had suffered a myocardial infarction (MI), i.e. the prevention of left ventricular (LV) remodeling, has so far not been specifically studied. The aim of the study was to investigate whether the D/I polymorphism of the ACE gene is associated with the incidence of post-MI LV remodeling in patients drawn from the 'Healing and Early Afterload Reducing Therapy' (HEART) Study. The ACE D/I polymorphism was characterized by the polymerase chain reaction (PCR) in 265 subjects from the 'Healing and Early Afterload Reducing Therapy' Study, a double-blind, placebo-controlled trial with the objective of determining whether early or delayed administration of the ACE-I, ramipril, in patients with acute anterior wall MI would be optimal in reducing LV enlargement. Selected frequencies for the ACE D and I alleles were 0.59 and 0.41 (placebo-high dose group), 0.56 and 0.44 (low dose-low dose group), and, 0.60 and 0.40 (high dose-high dose group), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for an association between genotype and outcome regarding LV size or function, nor with the initial blood pressure response after ACE-I administration (adjusted for covariates). Our data provide no evidence for an association of the ACE D/I polymorphism with the risk of LV remodeling post-MI in the presence of ACE-I therapy, and therefore do not suggest that differential clinical efficacy of ACE-inhibitors is related to this genetic marker.