Contrasting genetic influence of PON 1 coding gene polymorphisms L55M and Q192R on individuals’ response to environmental agents

Background: Paraoxonase (PON1) is an A-esterase capable of hydrolyzing the active metabolites (oxons) of many organophosphorus (OP) insecticides. Human PON1 displays two polymorphisms in the coding region (Q192R and L55M) and several polymorphisms in the promoter and the 30-UTR regions. Animal studies have shown that PON1 is an important determinant of OP toxicity though a direct satisfactory verification in humans is still lacking.Aim: To investigate the impact of polymorphisms in the PON1 coding region (Q192R and L55M) on individual sensitivity to OP poisoning.Subjects and methods: This study enrolled 42 subjects (21 females and 21 males, age range 1.5– 53 years) diagnosed of acute OP poisoning. They were classified into 4 grades according to manifestations. All subjects were genotyped for the PON1 gene polymorphisms; Q192R and L55M using RFLP-PCR, then genotype frequencies were compared between different OP grades.Results: Genotype frequency distribution of PON1 L55M polymorphism among different OP poisoning grades revealed no significant difference (p>0.05) between the four grades. In contrast, frequency distribution of PON1 Q192R polymorphism showed a highly significant (p< 0.001) difference between different grades of OP poisoning, with QQ genotype predominating in grade 4 with a frequency of 66.7%, followed by QR genotype (33.3%), while the RR and QR genotypes were similarly distributed in grade 1 with a frequency of 50% for each.Conclusion: The current results suggest a possible association between QQ genotype and poor OP poisoning prognosis.KEYWORDS Paraoxonase; L55M; Q192R; Organophosphate; Poisoning grad

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified