The Correlation Between Interleukin28B Genetic Variation And Susceptibility To Hepatitis C And Distribution Characteristics Of HCV Genotypes In China

ObjectiveHepatitis C virus is widely prevalent in the world and remains a worldwide public health problem. HCV infection contributes to progressive liver disease, cirrhosis, and hepatocellular carcinoma. It is mainly associated with two factors, the host and virus. The study aimed to study the correlation between single nucleotide polymorphisms of interleukin28B of the host and susceptibility to hepatitis C in China. At the same time, we detected HCV genotypes of2317Chinese hepatitis C patients in order to better understand the epidemiological characteristics of HCV and provided valuable information of HCV infection in China.MethodsNine SNPs(rs8099917、rs12980275、rs8105790、rs11881222、rs8103142、 rs28416813、rs4803219、rs12979860、rs7248668) located in and around the IL28B gene were genotyped in122patients infected with HCV and205healthy controls using SNaPshot assay. Pair-wise linkage disequilibrium between the nine SNPs was analyzed and rs8099917was selected as the tag SNP. The differences in rs8099917genotypes and allele frequencies between the two groups were analyzed by statistics.At the same time, HCV genotyping was conducted for2317patients from12different provinces of China by nucleotide sequencing of the C/El region of HCV genome. Then the geographical distribution and correlation between host factors and HCV genotype were analyzed.Results1. The nine SNPs were in strong linkage disequilibrium with each other (r2>0.80).The genotype frequencies of TG and TT of rs8099917in HCV patients were22.95%and77.05%, respectively; and13.66%and86.34%, respectively in healthy controls. The allele frequencies of G and T were11.48%and88.52%, respectively in HCV patients; and6.83%and93.17%, respectively in healthy controls. There were significant differences in both genotype distribution and allele frequency of rs8099917polymorphism between the two groups(P<0.05).2. Among the2317samples, four HCV genotypes(1,2,3,6) and twelve subtypes were detected. In general, subtypes lb (59.82%) and2a (29.35%) were dominant, followed by subtypes3b (4.23%),3a (2.85%) and6a (2.68%). Meanwhile, subtypes1a,2b,6b,6j,6n,6u and6v were detected at frequency1.07%as a whole.A significant distribution difference was observed according to different regions. In general, subtypes lb and2a were still dominant in most regions. But subtypes3a,3b and6a were increasing, especially in southwest China. Besides, subtypes1a,2b,6b,6j,6n,6u and6v were more likely to be detected in the southwest too.There was a significant difference of HCV genotype distribution between males and females. Frequencies of subtypes3a and3b in males is higher than that in females(P<0.05). A variation in the distribution of HCV genotypes among different age groups was observed. Subtypes3a,3b and6a were more likely to be detected in21-60age groups than in those<21and>60groups. In individuals21-60years old, frequencies of subtypes3a,3b and6a were higher in<40groups than those>40groups(P<0.05).Conclusion1. The single nucleotide polymorphisms of IL28B were correlated with susceptibility to HCV infection among Chinese population. G allele of rs8099917was associated with a higher risk of HCV infection.2. HCV genotypes lb and2a still dominated in most regions of China. Regional differences existed in the genotype distribution.The detection rates of3a,3b and6a and rare subtypes(la,2b,6b,6j,6n,6uand6v) were increased remarkably. This distribution characteristics were especially obvious in southwest China. And this changing pattern of HCV infection had been spreading to the whole China.