Low-density lipoprotein receptor genetic polymorphism in chronic hepatitis C virus Egyptian patients affects treatment response.
OBJECTIVE
To correlate a genetic polymorphism of the low-density lipoprotein (LDL) receptor with antiviral responses in Egyptian chronic hepatitis C virus (HCV) patients.


METHODS
Our study included 657 HCV-infected patients with genotype 4 who received interferon-based combination therapy. Patients were divided into two groups based on their response to therapy: 356 were responders, and 301 were non-responders. Patients were compared to 160 healthy controls. All patients and controls underwent a thorough physical examination, measurement of body mass index (BMI) and the following laboratory tests: serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total bilirubin, direct bilirubin, prothrombin time, prothrombin concentration, INR, complete blood count, serum creatinine, fasting blood sugar, HCV antibody, and hepatitis B surface antigen. All HCV patients were further subjected to the following laboratory tests: HCV-RNA using quantitative polymerase chain reaction (PCR), antinuclear antibodies, thyroid-stimulating hormone, an LDL receptor (LDLR) genotype study of LDLR exon8c.1171G>A and exon10c.1413G>A using real-time PCR-based assays, abdominal ultrasonography, ultrasonographic-guided liver biopsy, and histopathological examination of liver biopsies. Correlations of LDL receptor polymorphisms with HAI, METAVIR score, presence of steatosis, and BMI were performed in all cases.


RESULTS
There were no statistically significant differences in response rates between the different types of interferon used or LDLR exon10c.1413G>A. However, there was a significant difference in the frequency of the LDL receptor exon8c.1171G>A genotype between cases (AA: 25.9%, GA: 22.2%, GG: 51.9%) and controls (AA: 3.8%, GA: 53.1% and GG: 43.1%) (P < 0.001). There was a statistically significant difference in the frequency of the LDLR exon 8C:1171 G>A polymorphism between responders (AA: 3.6%, GA: 15.2%, GG: 81.2%) and non-responders (AA: 52.2%, GA: 30.6%, GG: 17.2%) (P < 0.001). The G allele of LDL receptor exon8c.1171G>A predominated in cases and controls over the A allele, and a statistically significant association with response to interferon was observed. The frequency of the LDLR exon8c.1171G>A allele in non-responders was: A: 67.4% and G: 32.6 vs A: 11.2% and G: 88.8% in responders (P < 0.001). Therefore, carriers of the A allele exhibited a 16.4 times greater risk for non-response. There was a significant association between LDL receptors exon8 c.1171G>A and HAI (P < 0.011). There was a significant association between LDL receptors exon8c.1171G>A and BMI. The mean BMI level was highest in patients carrying the AA genotype (28.7 ± 4.7 kg/m(2)) followed by the GA genotype (28.1 ± 4.8 kg/m(2)). The lowest BMI was the GG genotype (26.6 ± 4.3 kg/m(2)) (P < 0.001). The only significant associations were found between LDL receptors exon8 c.1171G>A and METAVIR score or steatosis (P < 0.001).


CONCLUSIONS
LDL receptor gene polymorphisms play a role in the treatment response of HCV and the modulation of disease progression in Egyptians infected with chronic HCV.
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Mazen
M
Naga
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Mona
M
Amin
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Dina
D
Algendy
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Ahmed
A
Elbadry
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
May
M
Fawzi
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Ayman
A
Foda
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Serag
S
Esmat
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Dina
D
Sabry
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Laila
L
Rashed
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Samia
S
Gabal
Mazen Naga, Mona Amin, Dina Algendy, Ahmed Elbadry, May Fawzi, Ayman Foda, Serag Esmat, Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
Manal
M
Kamal
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004534:Egypt; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011973:Receptors, LDL / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C573412:LDLR protein, human; D011973:Receptors, LDL; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
Egypt; Genetic polymorphisms; Hepatitis C virus; Hepatitis C virus response to treatment; Low-density lipoprotein receptor