1) ) -image taken from: ...

1
overing Bio-markers to improve quality of -Post-natal Depression Management 1) )http://www.nhs.uk/conditions/Postnataldepression/Pages/Introduction.aspx -Image taken from: http://www.ohm-hochschule.de/fileadmin/Fachbereiche/ac/Neubearbeitung_der_Homepage/Fachgebiete/ Biochemie/Bilder/LightCycler.jpg Introduction Post-natal depression (PND) affects 1 in 7 women in the western world making no distinction between ethnicity, with highest levels reported in teenagers (1). Identifying a means of finding people who are at risk of PND before they develop symptoms can be essential for the health and psychological development of both mother and child. PND possibly originates from inappropriate responses to stressors by the hypothalamic pituitary axis (HPA) which is influenced by genetic variation. Aim: To investigate genetic signatures known to be associated with depression (i.e.RS110402). Thereafter establishing a correlation between mutants for particular alleles (single nucleotide polymorphisms (SNPs)) and evidence for risk of PND (based on Edinburgh Post-natal depression scale (EPDS) scores i.e. above 10). Method 140 patients recruited to take a questionnaire (EPDS) and give blood sampl scores taken post-natally 2-8 weeks later (Engineer.N). DNA extracted from blood samples (Darwin.L). DNA analysed with appropriate probes and primers for SNP RS110402 using Ro -relying on principles of real-time polymerase chain reaction (PCR) and Fluo Transfer (FRET) with subsequent melting curve analysis. Grammatopoulos.D 1,2 , Engineer.N 3 , Pandey.S 2 , Darwin.L 1,2 , Khan.S (2012) 1,Warwick Medical School, University of Warwick, Coventry, UK 2,Dept. of Clinical Biochemistry, UHCW NHS, Trust Coventry, UK 3,Dept. of Obstetrics and Gynaecology, UHCW NHS Trust, Coventry, UK Warwick Medical School, Gibbet Hill Road, Coventry, CV4 7ES [email protected] Conclusion: Statistically based on this group size (140 patients) Rs110402 was inadequate in use as a bio-marker: 34 of the cohort had PND according to EPDS scores. Through our analysis 24 (17%) homozygous mutants were discovered when looking for Rs110402 variants but only 3 of these were shown to correlate with PND risk (an overall 8.8% success rate at predicting PND). Future Potential Previous research by team members into other SNPs of the Corticotropin Releasing Hormo Receptor 1 (CRHR1) family has proven successful therefore future work may involve cont search for successful genetic variants which strongly correlate with depression. Ultimately the goal is to find a particular combination of genetic signatures which ca screen pregnant mothers allowing the NHS to tailor healthcare so that severe psycholog physical harm can be prevented.. C-C (Homozygous WT) C-T (Heterozygous) T-T (Homozygous mutant) 0 5 10 15 20 25 30 35 40 45 SNP (genetic variation) Percentage of Cohot Non- Depress ed Depress ed 21 3 Resul ts

Upload: ava-bence

Post on 16-Dec-2015

217 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: 1) ) -Image taken from:  hochschule.de/fileadmin/Fachbereiche/ac/Neubearbeitung_der_Homepage/Fachgebiete/Biochemie/Bilder/LightCycler.jpg

Discovering Bio-markers to improve quality of life-Post-natal Depression Management

1) )http://www.nhs.uk/conditions/Postnataldepression/Pages/Introduction.aspx -Image taken from: http://www.ohm-hochschule.de/fileadmin/Fachbereiche/ac/Neubearbeitung_der_Homepage/Fachgebiete/Biochemie/Bilder/LightCycler.jpg

Introduction Post-natal depression (PND) affects 1 in 7 women in the western world making no distinction between ethnicity, with highest levels reported in teenagers (1). Identifying a means of finding people who are at risk of PND before they develop symptoms can be essential for the health and psychological development of both mother and child. PND possibly originates from inappropriate responses to stressors by the hypothalamic pituitary axis (HPA) which is influenced by genetic variation. Aim: To investigate genetic signatures known to be associated with depression (i.e.RS110402). Thereafter establishing a correlation between mutants for particular alleles (single nucleotide polymorphisms (SNPs)) and evidence for risk of PND (based on Edinburgh Post-natal depression scale (EPDS) scores i.e. above 10).

Method 140 patients recruited to take a questionnaire (EPDS) and give blood samples with further EPDS scores taken post-natally 2-8 weeks later (Engineer.N). DNA extracted from blood samples (Darwin.L). DNA analysed with appropriate probes and primers for SNP RS110402 using Roche Lightcyler-relying on principles of real-time polymerase chain reaction (PCR) and Fluorescence Resonance Energy Transfer (FRET) with subsequent melting curve analysis.

Grammatopoulos.D1,2, Engineer.N3, Pandey.S2, Darwin.L1,2, Khan.S (2012)1,Warwick Medical School, University of Warwick, Coventry, UK2,Dept. of Clinical Biochemistry, UHCW NHS, Trust Coventry, UK

3,Dept. of Obstetrics and Gynaecology, UHCW NHS Trust, Coventry, UK

Warwick Medical School, Gibbet Hill Road, Coventry, CV4 [email protected]

Conclusion:Statistically based on this group size (140 patients) Rs110402 was inadequate in use as a bio-marker: 34 of the cohort had PND according to EPDS scores. Through our analysis 24 (17%) homozygous mutants were discovered when looking for Rs110402 variants but only 3 of these were shown to correlate with PND risk (an overall 8.8% success rate at predicting PND).

Future Potential Previous research by team members into other SNPs of the Corticotropin Releasing Hormone Receptor 1 (CRHR1) family has proven successful therefore future work may involve continuing the search for successful genetic variants which strongly correlate with depression. Ultimately the goal is to find a particular combination of genetic signatures which can be used to screen pregnant mothers allowing the NHS to tailor healthcare so that severe psychological and physical harm can be prevented..

C-C (Homozygous WT) C-T (Heterozygous) T-T (Homozygous mutant)0

5

10

15

20

25

30

35

40

45

SNP (genetic variation)

Perc

enta

ge o

f Coh

ot

Non-Depressed

Depressed

21 3

Results