EVIDENCE FOR HAPLOTYPE-BASED ASSOCIATION IN SLE AT THE C-REACTIVE PROTEIN LOCUS: POPULATION-BASED AND FAMILY-BASED ASSOCIATION STUDIES

Systemic lupus erythematosus (SLE) is a major public health problem in the U.S. Cardiovascular disease (CVD) risk increases significantly in SLE patients, resulting in serious morbidity and mortality. Accelerated atherosclerosis and markedly higher prevalence of CVD risk factors (intermediate phenotypes) are thought to directly contribute to these consequences. Given the significant mortality and morbidity associated with SLE and high prevalence of CVD in SLE, identifying genetic variation associated with both SLE risk and intermediate phenotypes of CVD is of significant importance.C-reactive protein (CRP) is a sensitive marker of inflammation. Increased CRP levels have been found to be associated with cardiovascular events in a large number of healthy populations and may contribute to atherosclerosis. The gene coding for CRP is located on chromosome 1q23.2, which falls within a linkage region thought to harbor a systemic lupus erythematosus (SLE) susceptibility gene. Moreover, two single nucleotide polymorphisms (SNPs) in the CRP gene have recently been shown to be associated with CRP levels and/or SLE risk in a British family-based cohort. This study was aimed to assess the genetic association between five CRP tagSNPs with SLE risk and intermediate phenotypes of CVD.The association between CRP and SLE risk, assessed in two independently-ascertained SLE cohorts, was tested in a case-control Caucasian sample of 337 SLE and 448 healthy controls from Pittsburgh and a family-based sample of 203 Caucasian SLE trios from Los Angeles. While none of the SNPs were found to be associated with SLE risk individually, global haplotype statistics revealed significant association (p < 0.000001) in the Pittsburgh cohort whereas all those haplotypes containing two potentially functional SNPs (-390 and +90) showed association with SLE risk in the Los. Angeles cohort (p = 0.01 - 0.06). The association study between CRP and intermediate phenotypes of CVD and stroke risk was tested in 237 of the SLE women from the Pittsburgh cohort. Four of the five tagSNPs (-861, -390, +90, and +838) examined revealed significant association with risk of intermediate phenotypes of CVD (p < 0.001 to 0.04). In summary, our data did not confirm previously observed individual SNP association with SLE, but suggested that unique haplotype combinations in the CRP gene may modify the risk of developing SLE, and that variation in CRP may contribute to the accelerated atherosclerosis in SLE

Fasting and postprandial soluble epoxide hydrolase-associated eicosanoids of remitted patients with eating disorder

Food aversion and food avoidance are significant challenges to overcome for patients with eating disorder such as anorexia nervosa. The epoxide hydrolase 2 gene (EPXH2) has been uncovered as a novel anorexia nervosa risk gene. We have also discovered EPHX2-associated eicosanoids derived from polyunsaturated fatty acids to be aberrant in patients with anorexia nervosa, suggesting that genetically moderated lipid metabolism may be an underlying factor in AN pathogenesis. The data presented in this article are related to the research article entitled “Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa” [1]. In this data article, we provide both fasting and non-fasting (postprandial) concentration of eicosanoids in remitted patients with eating disorder and healthy controls. The data provides information on quantitative bioactive lipid mediators in fasting as well as non-fasting states, allowing inference of lipid metabolism associated with food consumption. The data set is made available to enable critical or extended analyzes. Keywords: Polyunsaturated fatty acid, Eicosanoid, Eating disorde

Food-Intake Normalization of Dysregulated Fatty Acids in Women with Anorexia Nervosa

Anorexia nervosa (AN) is a psychiatric disorder affected by psychological, environmental, and biological factors. Individuals with AN avoid high-fat, high-calorie diets and have shown abnormal metabolism of fatty acids (FAs), which are essential for brain and cognitive/neuropsychiatric health. To clarify the relationship between FAs and AN, fasting and postprandial plasma FAs in AN patients and age-matched control women were analyzed via mass-spectrometry. Clinical phenotypes were assessed using Becker Anxiety Inventory and Becker Depression Inventory. AN patients and controls exhibited different FA signatures at both fasting and postprandial timepoints. Lauric acid, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and alpha-linoleic acid (ALA) were higher in AN than in controls (lauric acid: 15,081.6 &plusmn; 14,970.2 vs. 8257.4 &plusmn; 4740.2 pmol/mL; ALA at fasting: 2217.7 &plusmn; 1587.6 vs. 1087.9 &plusmn; 821.2 pmol/mL; ALA at postprandial: 1830.9 &plusmn; 1115.6 vs. 1159.4 &plusmn; 664.7 pmol/mL. EPA: 33,788.3 &plusmn; 17,487.5 vs. 22,860.6 &plusmn; 12,642.4 pmol/mL; DPA: 32,664.8 &plusmn; 16,215.0 vs. 20,969.0 &plusmn; 12,350.0 pmol/mL. FDR-adjusted p-values &lt; 0.05). Food intake and AN status modified the correlations of FAs with body mass index (BMI), depression, and anxiety. Desaturases SCD-18 and D6D showed lower activities in AN compared to controls. Altered FA signature, specifically correlations between elevated n-3 FAs and worsened symptoms, illustrate metabolic underpinnings in AN. Future studies should investigate the mechanisms by which FA dysregulation, specifically elevated n-3 FAs, affects AN risk and outcome

Soluble Epoxide Hydrolase Is Associated with Postprandial Anxiety Decrease in Healthy Adult Women

The metabolism of bioactive oxylipins by soluble epoxide hydrolase (sEH) plays an important role in inflammation, and sEH may be a risk modifier in various human diseases and disorders. The relationships that sEH has with the risk factors of these diseases remain elusive. Herein, sEH protein expression and activity in white blood cells were characterized before and after a high-fat meal in healthy women (HW) and women with anorexia nervosa (AN). sEH expression and sEH activity were significantly correlated and increased in both groups two hours after consumption of the study meal. Fasting sEH expression and activity were positively associated with body mass index (BMI) in both groups, while an inverse association with age was found in AN only (p value &lt; 0.05). sEH was not associated with anxiety or depression in either group at the fasting timepoint. While the anxiety score decreased after eating in both groups, a higher fasting sEH was associated with a lower postprandial anxiety decrease in HW (p value &lt; 0.05). sEH characterization using direct measurements verified the relationship between the protein expression and in vivo activity of this important oxylipin modulator, while a well-controlled food challenge study design using HW and a clinical control group of women with disordered eating elucidated sEH&rsquo;s role in the health of adult women

Soluble Epoxide Hydrolase Is Associated with Postprandial Anxiety Decrease in Healthy Adult Women

The metabolism of bioactive oxylipins by soluble epoxide hydrolase (sEH) plays an important role in inflammation, and sEH may be a risk modifier in various human diseases and disorders. The relationships that sEH has with the risk factors of these diseases remain elusive. Herein, sEH protein expression and activity in white blood cells were characterized before and after a high-fat meal in healthy women (HW) and women with anorexia nervosa (AN). sEH expression and sEH activity were significantly correlated and increased in both groups two hours after consumption of the study meal. Fasting sEH expression and activity were positively associated with body mass index (BMI) in both groups, while an inverse association with age was found in AN only (p value &lt; 0.05). sEH was not associated with anxiety or depression in either group at the fasting timepoint. While the anxiety score decreased after eating in both groups, a higher fasting sEH was associated with a lower postprandial anxiety decrease in HW (p value &lt; 0.05). sEH characterization using direct measurements verified the relationship between the protein expression and in vivo activity of this important oxylipin modulator, while a well-controlled food challenge study design using HW and a clinical control group of women with disordered eating elucidated sEH’s role in the health of adult women