Relation between Fatty Acid Composition and Clinical Status or Genotype in Cystic Fibrosis Patients

Abstract

Objective: To evaluate the relation of clinical parameters and genotype with the serum phospholipid fatty acid (FA) composition in cystic fibrosis (CF) patients. Methods: A blood sample was taken from CF patients with stable pulmonary disease for the determination of phospholipid FA composition and vitamin E concentration who had been followed for at least 6 months at our Cystic Fibrosis Centre. Genotype, age, pancreatic function, nutritional status, caloric intake, pulmonary function and presence of Pseudomonas colonization, liver disease or diabetes mellitus were recorded. Patients were divided into two groups according to their genotype (group A: mutation class I, II, or III, group B: mutation class IV, V). Results: CF patients (group A and B together) have significantly lower docosahexaenoic acid (DHA) (p < 0.007) and linoleic acid (LA) (p < 0.0001) and higher dihomogammalinolenic acid (DHGLA) (p < 0.0001), oleic acid (OA) (p < 0.0001) and Mead acid (MA) (p < 0.0001), resulting in an increased ratio of arachidonic acid (AA)/DHA (p < 0.004), MA/AA (p < 0.0001) and OA/LA (p < 0.0001). Compared to group B, group A had a lower LA (p < 0.002) and a higher DHGLA (p < 0.002), 22:4ω–6 (p < 0.03), 22:5ω–6 (p < 0.03) and 20:3ω–9 (p < 0.04). There was however no significant difference between the groups for age, pulmonary function, nutritional status and vitamin E concentration. There was no relation of serum FA composition with nutritional status, caloric intake, pancreatic function, gender, pulmonary function, Pseudomonas colonization or diabetes mellitus. In CF with liver disease the DHA was lower than in the patients of the same genotype. Conclusion: FA disturbances are more pronounced in the severe CF genotypes and the presence of CF-related liver disease. Future studies on supplementation should take these parameters into account.

Persistence of Essential Fatty Acid Deficiency in Cystic Fibrosis Despite Nutritional Therapy

“…As expected, development of CFRLD resulted in aggravation of the EFA deficiency status (12). It should be paid attention to the progressive deterioration of endocrine pancreatic function as revealed by changes in fasting plasma glucose and insulin levels and by the high proportion of patients (25%) developing clinical diabetes mellitus over a follow-up period of 8 y.…”

“…This profile is different from that usually present in typical nutritional EFA deficiency (9). Fatty acid composition may be influenced by genetic factors as shown in murine models (10,11) or in humans (12). The role played by pancreatic insufficiency may also be especially relevant because fat malabsorption persists in many patients despite pancreatic enzyme replacement (13).…”

DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity

“…Peaks were identifi ed by UV detection at 205 nm, and their identity was determined by comparing peak retention time with that of unlabeled FAME standards. Radiolabeled peaks were quantifi ed using a ␤ -RAM scintillation detector (counting effi ciency >90% for 14 C with 5 CPM background) coupled to the HPLC instrument. Results are expressed as percentage of total measured counts in the sample.…”

Essential Fatty Acid Deficiency in Cystic Fibrosis

“…Most studies describe an increased OA, EPA and DHGLA and a decreased DHA and LA concentration [37,38]. The ratio of AA/DHA is increased suggesting a proinflammatory state [37,38].…”