PubMed Health⌕ Search

Biomedical subjects

Jennifer K Pai

Publications and source records attributed to Jennifer K Pai.

8 recordsLinked to original sources
PubMed2007

Effects of lymphotoxin-alpha gene and galectin-2 gene polymorphisms on inflammatory biomarkers, cellular adhesion molecules and risk of coronary heart disease.

The pro-inflammatory cytokine LTA (lymphotoxin-alpha) has multiple functions in regulating the immune system and may contribute to inflammatory processes leading to CHD (coronary heart disease). The aim of the present study was to investigate whether the common C804A (resulting in a Thr(26)-->Asp amino acid substitution) and A252G polymorphisms of the LTA gene and the C3279T polymorphism of the galectin-2 (LGALS2) gene, which affects LTA secretion, are associated with inflammatory parameters and cell adhesion molecules, and whether these polymorphisms are related to CHD in American women and men. We conducted a prospective nested case-control study within the Nurses' Health Study and Health Professionals Follow-Up Study. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed CHD during 8 and 6 years of follow-up respectively, and we matched controls 2:1 based on age and smoking. The LGALS2 gene variant was significantly associated with a decreased risk of CHD in women [odds ratio (95% confidence interval), 0.70 (0.50-0.97); P=0.03]. In addition, the LGALS2 polymorphism was directly associated with CRP (C-reactive protein) levels in cases from both studies (P<0.05). The LTA gene polymorphisms were directly associated with levels of sTNFRs (soluble tumour necrosis factor receptors) and VCAM-1 (vascular cell adhesion molecule-1) in both women and men with CHD (P<0.05). However, no overall effect was demonstrated between LTA gene polymorphisms and risk of CHD.

Age Factors↗
PubMed2005

Moderate alcohol consumption and lower levels of inflammatory markers in US men and women.

OBJECTIVE: Moderate alcohol consumption is associated with substantially lower risk of cardiovascular disease (CVD). We assessed the relationship between alcohol intake and inflammatory markers to partially explain this beneficial effect. METHODS AND RESULTS: From two large prospective studies, we sampled 959 healthy male and 473 healthy female health professionals with reported alcohol intake. Markers of inflammation were soluble tumor necrosis factor-alpha receptors 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein (CRP), and interleukin-6 (IL-6). We found significant inverse linear trends for sTNF-R1 (p-trend<0.001 men; 0.03 women) and sTNF-R2 (p-trend=0.002 men; 0.08 women) with increasing alcohol intake. Compared to non-drinkers, men who consumed on average 1-2 drinks/day had 26% lower CRP (-0.66 mg/L, p=0.13), and 36% lower IL-6 (-1.12 pg/ml, p=0.02) levels. Among women, a similar though stronger association was observed at half drink per day. Compared to non-drinkers, both men and women who consumed 1-2 drinks/drinking day had significantly lower sTNF-R1 (-9% in men, -6% in women) and sTNF-R2 (-7% in men, -6% in women) levels as well as lower CRP (-10% in men, -32% in women) and IL-6 (-45% in men, -27% in women) levels. CONCLUSIONS: Alcohol in moderation is associated with lower levels of inflammatory markers and may lower risk of CVD through these mechanisms.

Acute-Phase Proteins↗
PubMed2005

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of coronary heart disease among US women.

OBJECTIVE: Genetic variation in CC-chemokine receptor-2 (CCR2) and -5 (CCR5), and their common haplotypes, acting through inflammatory responses, may affect atherosclerosis and risk of coronary heart disease (CHD). METHOD AND RESULTS: We examined seven common variants in the CCR2 and CCR5 loci and risk of CHD among women in the Nurses' Health Study. During 8 years of follow-up, we documented 248 incident cases of nonfatal myocardial infarction and fatal CHD, and matched controls 2:1 based on age and smoking. The distribution of alleles was similar between cases and controls. The haplotype-specific odds ratios (ORs) were not statistically significant nor was the globally-adjusted p-value (p=0.61). However, there was a statistically significant association for CCR5-Delta32 and A58755G (rs2856758) between cases and controls comparing age of onset <55 and >or=55 years. For Delta32, the OR for having the variant was 0.12 (0.02-0.76) for age <55, and 1.14 (0.69-1.88) for age >or=55 years (p, interaction=0.04). The CCR5-Delta32 was in linkage disequilibrium with 58755G, and a similar association was observed for having the 58755G. CONCLUSIONS: In this population, CCR2-CCR5 haplotypes were not associated with risk of CHD. However, our data suggest a strong inverse association for certain CCR5 variants and early age of CHD onset.

Adult↗
PubMed2005

Peroxisome proliferator-activated receptor-gamma2 P12A polymorphism and risk of coronary heart disease in US men and women.

OBJECTIVE: Activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma) improves insulin sensitivity and exerts antiatherogenic effects. A common alanine for proline substitution at codon 12 in the PPARG2 gene is related to lower receptor activity. Studies suggest that the A12 allele is associated with reduced risk of type 2 diabetes; however, data on the risk of coronary heart disease (CHD) are scarce and controversial. METHODS AND RESULTS: We examined the relationship between PPARG2 P12A and CHD risk in women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) in nested case control settings. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed nonfatal myocardial infarction (MI) or fatal CHD during 8 and 6 years of follow-up, respectively. Using risk-set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. The relative risk (RR) of nonfatal MI or fatal CHD of carriers compared with noncarriers of the A12 allele was 1.17 (95% CI, 0.82 to 1.68) among women and 1.44 (95% CI, 1.00 to 2.07) among men (pooled RR, 1.30 [95% CI, 1.00 to 1.67]). We found a significantly increased risk associated with the A12 allele among individuals with a body mass index > or =25 kg/m2 (women: RR, 1.88; 95% CI, 1.01 to 3.50; men: RR, 1.55; 95% CI, 0.92 to 2.60; pooled: RR, 1.68; 95% CI, 1.13 to 2.50) but not among those <25 kg/m2 (pooled RR, 0.86; 95% CI, 0.37 to 1.97; P heterogeneity overweight versus nonoverweight 0.16). CONCLUSIONS: These data do not support the hypothesis that the A12 allele is associated with a decreased risk of CHD. The potential interaction between PPARG2 P12A, overweight, and increased CHD risk needs further evaluation.

Adult↗
PubMed2004

Inflammatory markers and the risk of coronary heart disease in men and women.

BACKGROUND: Few studies have simultaneously investigated the role of soluble tumor necrosis factor alpha (TNF-alpha) receptors types 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein, and interleukin-6 as predictors of cardiovascular events. The value of these inflammatory markers as independent predictors remains controversial. METHODS: We examined plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein as markers of risk for coronary heart disease among women participating in the Nurses' Health Study and men participating in the Health Professionals Follow-up Study in nested case-control analyses. Among participants who provided a blood sample and who were free of cardiovascular disease at baseline, 239 women and 265 men had a nonfatal myocardial infarction or fatal coronary heart disease during eight years and six years of follow-up, respectively. Using risk-set sampling, we selected controls in a 2:1 ratio with matching for age, smoking status, and date of blood sampling. RESULTS: After adjustment for matching factors, high levels of interleukin-6 and C-reactive protein were significantly related to an increased risk of coronary heart disease in both sexes, whereas high levels of soluble TNF-alpha receptors were significant only among women. Further adjustment for lipid and nonlipid factors attenuated all associations; only C-reactive protein levels remained significant. The relative risk among all participants was 1.79 for those with C-reactive protein levels of at least 3.0 mg per liter, as compared with those with levels of less than 1.0 mg per liter (95 percent confidence interval, 1.27 to 2.51; P for trend <0.001). Additional adjustment for the presence or absence of diabetes and hypertension moderately attenuated the relative risk to 1.68 (95 percent confidence interval, 1.18 to 2.38; P for trend = 0.008). CONCLUSIONS: Elevated levels of inflammatory markers, particularly C-reactive protein, indicate an increased risk of coronary heart disease. Although plasma lipid levels were more strongly associated with an increased risk than were inflammatory markers, the level of C-reactive protein remained a significant contributor to the prediction of coronary heart disease.

Adult↗
PubMed2004

Kidney dysfunction, inflammation, and coronary events: a prospective study.

Kidney dysfunction and high C-reactive protein (CRP) levels are independently associated with coronary events. However, it is unclear whether the risk of coronary events associated with decreased kidney function is at least partially mediated by inflammation and whether the association between inflammatory biomarkers and coronary events is influenced by level of kidney function. With the use of a prospective, nested, case-control study design, the association among kidney function, inflammatory biomarker levels, and coronary events was studied. A total of 244 women who were participants in the Nurses' Health Study and had no history of cardiovascular disease received a diagnosis of an incident coronary event (defined as nonfatal myocardial infarction or death as a result of coronary disease) during the follow-up period from 1990 to 1998 and were matched to 486 control subjects. Serum creatinine and inflammatory biomarker levels were measured in blood samples collected in 1989. Creatinine clearance (CrCl) was estimated using creatinine, age, weight, and height. In multivariate analyses, the odds ratio (OR) for a coronary event in women with an estimated CrCl <60 ml/min was 2.33 (95% confidence interval [CI], 1.01 to 5.38) compared with those with a CrCl > or =90 ml/min. When soluble tumor necrosis factor receptor (sTNFR) I and II levels were added into this model individually, the observed OR for women with CrCl <60 ml/min was attenuated. In analyses stratified by estimated CrCl, higher high-sensitivity CRP (hs-CRP), IL-6, and sTNFR I and II levels each were significantly associated with an increased odds of coronary events in women with an estimated CrCl < or =74 ml/min but not in women with an estimated CrCl > or =75 ml/min. The OR per 5-mg/L unit increase in hs-CRP was 1.68 (95% CI, 1.13 to 2.52) for women with an estimated CrCl < or =74 ml/min, compared with 1.23 (95% CI, 0.86 to 1.76) and 0.99 (95% CI, 0.76 to 1.29) for women with an estimated CrCl 75 to 89 and > or =90 ml/min, respectively (P = 0.004 for interaction). In conclusion, kidney dysfunction is associated with an increased odds of coronary events, and inflammation, as assessed by higher sTNFR I and II levels, may mediate some of this risk. Higher inflammatory biomarkers levels, specifically, hs-CRP, IL-6, and sTNFR I and II, were significantly associated with coronary events only in women with reduced kidney function. These findings warrant further investigation in other populations.

Adult↗