Identification of genetic variants the CCKAR gene and based on body measurement and carcass quality characteristics in Qinchuan beef cattle (Bos taurus)

BACKGROUND: This study aimed to explore genetic polymorphisms of the CCKAR gene and their relationship with the growth and development of Qinchuan cattle which could be used as molecular markers for the improvement of the breeding of Qinchuan cattle. RESULTS: Here, we have identified seven single nucleotide polymorphisms (SNPs) at loci g. 1463 C>G; g. 1532 T>A; g. 1570 G>A; g. 1594 C>A; g. 1640 T>C; g. 1677 G>C; and g. 1735 C>T in the coding region of the bovine CCKAR gene. The frequencies identified on allelic and genotypic characteristics have shown that all seven SNPs diverged from the Hardy-Weinberg-Equilibrium. The SNP2, SNP3, SNP6 and SNP7 had the lowest polymorphism information content values, and remaining SNPs were found to be moderate (0.25 < PIC < 0.50). The genotype CG in SNP1 at loci g.1463 C>G had the greatest association with WH, HW, CD and CCF, while the genotype TA at the very same loci was associated with BFT, ULA and IMF content in Qinchuan cattle. The CCKAR gene expression level in adipose tissue, small intestine, liver and skeleton muscle was found to be higher, whereas, the expression level of mRNA in organs of other digestive system including reticulum, abomasum and omasum was moderate. Some expression of CCKAR mRNA was found in the large intestine, kidney and rumen. CONCLUSIONS: In summary, our finding suggested that the CCKAR gene could be used as a potential candidate for the improvement of carcass quality and body measurements of Qinchuan cattle.

Pre-treatment predictors of response for assessing outcomes to standard treatment in infection with HCV genotype 3.

OBJECTIVE: To determine the role of pre-treatment predictors of response in assessing outcomes to standard treatment in HCV genotype 3. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medicine, KRL General Hospital, Islamabad, from December 2004 to December 2006. METHODOLOGY: All patients with positive anti-HCV and PCR genotype 3a were recruited and written and informed consent was taken. Patients were treated with standard Interferon plus Ribavirin therapy (IFN alpha-2a, 3MU t.i.w 24 weeks plus Ribavirin 1000-1200 mg/day) for 6 months. The effect of pre-treatment factors influencing outcome i.e. age, gender, weight, baseline ALT, necroinflammatory grade, fibrosis and steatosis on the final outcome were further analyzed by univariate logistic regression analysis. RESULTS: Response rates to standard Interferon plus Ribazole therapy were studied in 190 patients. The end-of-treatment complete response (EOTCR) was seen in 81% (n=155) of the patients, whereas 17% (n=33) were non-responders (NR). Sustained viral response (SVR) was seen in 58% (n=112) patients and 24% (n=45) were relapsers. SVR was higher in patients without steatosis (OR=2.52, 95% CI=1.356- 4.71, p=0.04). Higher SVR was seen in patients weighing less than 65 kg, as compared with weight>65 kg (OR=2.277, 95% CI=1.246-4.161, p=0.007). The other variables were not found to be significantly associated with improved SVRs. CONCLUSION: Out of the studied predictors, body weight and presence of steatosis, were statistically related to treatment outcome. Pre-treatment host factors can predict response to treatment that can help in individualizing treatment and patient selection and optimize treatment outcomes.

Response rates to standard interferon treatment in HCV genotype 3a.

BACKGROUND: Chronic Hepatitis C infection infects almost 130 to 170 million or approximately 2.2-3% of world's population. HCV is one of the main causes of chronic liver disease leading to progressive liver injury, fibrosis, cirrhosis and liver cancer. It is also one of the leading indications for liver transplantation worldwide. The objective of the study was to determine the response of treatment with standard Interferon and Ribazole in treatment naïve Hepatitis C infected patients. METHODS: This quasi-experimental study was carried out at the Department of Medicine, KRL General Hospital Islamabad, from January 2003 to January 2005. A total of 250 patients were enrolled in this descriptive study. All patients were anti HCV positive, PCR positive for HCV RNA and had 3a genotype. A non-probability purposive sampling technique was applied to collect data. After taking a written and informed consent; specially designed performa containing the patient profile, family transmission, and baseline laboratory values was filled. Patients were treated with a set protocol of Interferon plus Ribavarin therapy (IFN alpha 2a, 3 mIU thrice weekly for 24 weeks plus Ribavarin 1,000 to 1,200 mg/day) for six months. Chi-Square tests were used to analyse the data. Primary end point was a sustained virological response (SVR) that is response assessed after six months of completion of treatment. RESULTS: Response rates to standard Interferon plus Ribazole therapy were studied over two years period. Out of the total of 250 patients, 60 patients were excluded; as 30 patients did not meet inclusion criteria, 23 patients were lost to follow. Seven patients declined treatment. Out of the 190 patients, 155 (81.6%) achieved End of Treatment Complete Response (EOTCR) whereas 35 (18.4%) were nonresponders (NR). These 155 patients, who showed complete response were followed for six months after the treatment to assess sustained viral response, which was seen in 112 (72.25%) patients whereas 43 (27.7%) were relapsers. Response rates were co-related with gender, baseline ALT and necro-inflammatory stage assessed by liver biopsy, probable risk factors and family history. CONCLUSION: Management of Hepatitis C with genotype 3a, with standard Interferon and Ribazole for six months showed lower SVR compared to that reported in previous international and local data.

Declining sustained virological response in hepatitis C.

OBJECTIVE: To determine the response of treatment with standard interferon and Ribazole in treatment naïve hepatitis C infected patients, with different grades of activity. DESIGN: A quasi-experimental study. PLACE AND DURATION OF STUDY: This study was carried out at the Department of Medicine, KRL General Hospital, Islamabad, from January 2001 to September 2004. PATIENTS AND METHODS: A total of 300 patients were enrolled. All patients were anti-HCV positive confirmed by device method, PCR positive and had 3a genotype. A specially-designed proforma containing the patient profile, family transmission, and baseline laboratory values was filled. All patients were treated according to a set protocol of Interferon plus ribavirin therapy (IFN alpha 2a, 3MU t.i.w 24 weeks plus ribavirin 1000 to 1200 mg/day) for six months. Chi-square tests were used to analyze the data. Primary end point was a sustained virological response (SVR) that is response assessed after six months of completion of treatment. RESULTS: Over a period of four years response rates to standard Interferon plus Ribazole therapy were studied. Out of the total 300 patients data was available for 161 patients as 60 patients were excluded and 79 patients are currently under treatment. Treatment was stopped in 3 patients due to serious side effects. In the 161 patients, 135 (83.8%), achieved response at the end of treatment at six months; End of Treatment Complete Response (EOTCR); and 26 (16.14%) were non-responders (NR). Out of the complete responders, 68 patients had been followed completely upto six months after the treatment to asses Sustained Viral Response (SVR) defined as undetectable HCV RNA in serum at the end of six months posttreatment follow-up. Sustained viral response was seen in 46 patients i.e. 68% ( CI: 57-79%) and 22(32.3%) were relapsers (those who developed recurrence of viremia after having achieved eradication at the end of six months treatment). Response rates are co-related with gender, baseline ALT and necroinflammatory stage assessed by liver biopsy, probable risk factors and positive family history. CONCLUSION: Management of hepatitis C with genotype 3a, with standard Interferon and Ribazole for six months appear to show declining SVR compared to that reported in previous international and local data.