Publications (54) View all
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Article: Influence of HLA-C Expression Level on HIV Control.
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ABSTRACT: A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.Science 04/2013; 340(6128):87-91. · 31.20 Impact Factor -
Article: Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts.
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ABSTRACT: Chinese translation Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person's lifetime risk for cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and persons with genetic variants near interleukin-28B (IL-28B), the genetic basis is not well-understood. To evaluate the host genetic basis for spontaneous resolution of HCV infection. 2-stage, genome-wide association study. 13 international multicenter study sites. 919 persons with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 persons with serum HCV antibodies and HCV RNA (persistence). Frequencies of 792 721 single nucleotide polymorphisms (SNPs). Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL-28B and included rs12979860 (overall per-allele OR, 0.45; P = 2.17 × 10-30) and 10 additional SNPs spanning 55 000 base pairs. On chromosome 6, allele frequency differences localized near genes for HLA class II and included rs4273729 (overall per-allele OR, 0.59; P = 1.71 × 10-16) near DQB1*03:01 and an additional 116 SNPs spanning 1 090 000 base pairs. The associations in chromosomes 19 and 6 were independent and additive and explain an estimated 14.9% (95% CI, 8.5% to 22.6%) and 15.8% (CI, 4.4% to 31.0%) of the variation in HCV resolution in persons of European and African ancestry, respectively. Replication of the chromosome 6 SNP, rs4272729, in an additional 745 persons confirmed the findings (P = 0.015). Epigenetic effects were not studied. IL-28B and HLA class II are independently associated with spontaneous resolution of HCV infection, and SNPs marking IL-28B and DQB1*03:01 may explain approximately 15% of spontaneous resolution of HCV infection. Office of AIDS Research, National Institutes of Health, and Frederick National Laboratory for Cancer Research.Annals of internal medicine 02/2013; 158(4):235-45. · 16.73 Impact Factor -
Article: Characterization of the HLA-C*07:01:01G allele group in European and African-American cohorts.
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ABSTRACT: The HLA-C*07:01:01G allele group consists of three nonsynonymous alleles, C*07:01:01, C*07:06 and C*07:18, plus C*07:01:02, which is synonymous to C*07:01:01. All of these alleles have identical exons 2, 3 and 4, but differ in exons 5 or 6. Therefore routine sequence-based typing (SBT) of exons 2 and 3 is unable to resolve these subtypes, resulting in ambiguous typing results in population and disease cohort studies. In the present study, we fully characterized C*07:01:01G subtypes in European and African Americans and examined their relative frequency distributions. In European Americans C*07:01:01G is predominantly represented by C*07:01:01 (94.4%), whereas C*07:01:02 (1.1%) and C*07:18 (4.5%) were detected relatively infrequently. In African Americans C*07:18 (42.4%) showed a high frequency similar to that of C*07:01:01 (44.7%) whereas C*07:06 was detected at a low frequency (4.7%). C*07:06 was found exclusively on B*44:03 carrying haplotypes in both ethnic groups, but C*07:18 showed multiple linkage relationships with HLA-B. These results demonstrate that C*07:01:01G as defined by routine SBT is a heterogeneous group of alleles, especially among individuals of African origin. If C*07:01:01G subtypes prove to bear divergent functional significance, it would be necessary to include these subtypes in routine HLA-C typing for clinical transplantation and disease association studies.Human immunology 04/2012; 73(7):715-9. · 2.55 Impact Factor -
Article: Distribution and forms of phosphorus in tidal flat sediments of the Yangtze Estuary and coast
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ABSTRACT: The distribution and forms of phosphorus (P) were investigated in the tidal flat sediments of the Yangtze Estuary and coast. The total P contents in surface sediments range from 18.0 to 31.4 μmol·g-1 along the southern coast. The spatial and temporal distribution of P in tidal flats is closely related to the location and pollution resources, especially in association with the variation of hydrodynamic conditions. Significant variations in the forms of P in different sites were observed. P bonded with Ca(Ca-P) is the dominant mineral form in all surface sediments, organic P(Org-P) is lower. Most P is of unstable form, suggesting that P has larger potential activity. P accumulation is the main behavior process between water and sediment in the coastal environment of the Yangtze Estuary.Science in China Series B Chemistry 04/2012; 44:190-196. · 1.20 Impact Factor -
Article: Lack of association between HLA class II alleles and in vitro replication capacities of recombinant viruses encoding HIV-1 subtype C Gag-protease from chronically infected individuals.
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ABSTRACT: It is unknown whether favorable HLA class II alleles may attenuate HIV-1 through selection pressure in a manner similar to that of protective HLA class I alleles. We investigated the relationship between HLA class II alleles and in vitro replication capacities of recombinant viruses encoding HIV-1 subtype C Gag-protease from chronically infected individuals. No associations were found between individual alleles and lower replication capacity, suggesting no significant HIV-1 attenuation by HLA class II-restricted Gag-specific CD4(+) T cell immune pressure.Journal of Virology 11/2011; 86(2):1273-6. · 5.40 Impact Factor
