Favorable genotypes

The most interesting aspect of the results of the study by Lee etal (2004) is that they also differ from those in a Caucasian population (Smeraldi, Benedetti Zanardi, 2002). The authors reported a more favorable natural history in those with the s/s genotype than in 1-allele carriers, which also differs from acute antidepressant responses in Caucasian populations. The frequencies of the s and 1 alleles among the Korean sample were approximately 86% and 14%, respectively, while the corresponding figures for Caucasians are 43% and 57% (Lesch etal, 1996). 

The TNF -308 polymorphism may be predictive of an individual patient s response to INF. In one study, 59 RA patients treated with INF after genotyping were classified into homozygotes for the TNF -308A allele (A/A 1.7%), heterozygotes (A/G 22%), and wild-type (G/G 76.3%) carriers of the allele. After 22 weeks of treatment with INF, the disease activity score (DAS a standardized measure of disease activity in RA) was used to assess response to INF. Patients without the A allele (81%) compared to patients with the A allele (42%) had a better response to INF as demonstrated by an improvement in the DAS (p 0.0009). Thus, this study suggested that RA patients who are carriers of the TNF=-30S G allele may have a more favorable response to INF (62). 

Several colorectal cancer studies have identified dilferences in TSER genotype between tumor and normal DNA. The frequency of the discrepancies range from 4% to 77.3% of TSER 2/ 3 heterozygotes [median 56% reviewed in (48)] and no allele bias is apparent (i.e., one repeat is not favored over the other). Curiously none of the studies have identified genotype discrepancies at a frequency of 15%, which would be consistent with the frequency of 18p loss of heterozygosity (LOH) in colorectal cancer. 

Treatment of patients with chronic HCV infection is recommended for those with an increased risk for progression to cirrhosis. The parameters for selection are complex. In those who are to be treated, however, the current standard of treatment is once-weekly pegylated interferon alfa in combination with daily oral ribavirin. Pegylated interferon alfa-2a and -2b have replaced their unmodified interferon alfo counterparts because of superior efficacy in combination with ribavirin, regardless of genotype. It is also clear that combination therapy with oral ribavirin is more effective than monotherapy with either interferon or ribavirin alone. Therefore, monotherapy with pegylated interferon alfa is recommended only in patients who cannot tolerate ribavirin. Factors associated with a favorable response to therapy include HCV genotype 2 or 3, absence of cirrhosis on liver biopsy, and low pretreatment HCV RNA levels. 

Recombination occurs primarily in germ cells of eukaryotes and during cell division in partially diploid prokaryotes. In general, recombination does not occur in mitosis of eukaryotic cells. However, recombination is an integral part of meiosis in which recombinant sperm and ova provide new genotypes and phenotypes in each generation which may be favored by natural selection. 

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