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Almost one third of the three million people in China suffering severe deafness are children, and 50% of these cases are believed to have genetic components to their etiology. Newborn hearing genetic screening can complement Universal Neonatal Hearing Screening for the diagnosis of congenital hearing loss as well as identifying children at risk for late-onset and progressive hearing impairment. The aim of this joint academic and Ministry of Health project was to prototype a cost effective newborn genetic screen in a community health setting on a city-wide level, and to ascertain the prevalence of variation at loci that have been associated with non-syndromic hearing loss. With the participation of 143 local hospitals in the city of Wuhan, China we screened 142,417 neonates born between May 2014 and Dec. 2015. The variants GJB2 c.235delC, SLC26A4 c.919-2A>G, and mitochondrial variants m.1555A>G and m.1494C>T were assayed using real time PCR. Newborns found to carry a variant were re-assayed by sequencing in duplicate. Within a subset of 707 newborns we assayed using real-time PCR and ARMS-PCR to compare cost, sensitivity and operating procedure. The most frequent hearing loss associated allele detected in this population was the 235delC variant in GJB2 gene. In total, 4289 (3.01%) newborns were found to carry at least one allele of either GJB2 c.235delC, SLC26A4 c.919-2A>G or two assayed MT-RNR1 variants. There was complete accordance between the real-time PCR and the ARMS PCR, though the real-time PCR had a much lower failure rate. Real-time PCR had a lower cost and operating time than ARMS PCR. Ongoing collaboration with the participating hospitals will determine the specificity and sensitivity of the association of the variants with hearing loss at birth and arising in early childhood, allowing an estimation of the benefits of newborn hearing genetic screening in a large-scale community setting.

There is considerable variability between individuals in susceptibility to infection by human immunodeficiency virus (HIV). Many social, clinical and genetic factors are known to contribute to the likelihood of HIV transmission, but there is little consensus on the relative importance and potential interaction of these factors. Additionally, recent studies of several variants in chemokine receptors have identified alleles that may be predictive of HIV transmission and disease progression; however the strengths and directions of the associations of these genetic markers with HIV transmission have markedly varied between studies. To better identify factors that predict HIV transmission in a Chinese population, 180 cohabiting serodiscordant couples were enrolled for study by the Henan Center for Disease Prevention and Control, and transmission and progression of HIV infection were regularly measured. We found that anti-retroviral therapy, education level, and condom use were the most significant factors in determining likelihood of HIV transmission in this study. We also assessed ten variants in three genes (CXCL12, CCR2, and CCR5) that have been shown to influence HIV transmission. We found two tightly linked variants in CCR2 and CCR5, rs1799864 and rs1800024, have a significant positive association with transmission as recessive models (OR>10, P value=0.011). Mixed effects models showed that these genetic variants both retained significance when assessed with either treatment or condom use. These markers of transmission susceptibility may therefore serve to help stratify individuals by risk for HIV transmission.

HIV/AIDS has the highest mortality among infectious diseases in China. In ongoing efforts to alleviate this crisis, the national government has placed great emphasis on efforts in Henan province where HIV-infected former plasma donors in the 1990s contributed to AIDS becoming a public health crisis. Concomitant with a national initiative focusing the use of pharmacogenetics for the better prediction of treatment response, we studied genetic variants with known pharmacokinetic phenotypes in a set of 298 HAART-treated (highly active antiretroviral therapy) patients infected with HIV from the Henan cohort. We measured the association of response to treatment, assessed as changes in CD4+ T cell counts after antiretroviral therapy, of five polymorphisms in four genes (CYP2B6, ABCB1/MDR1, ABCG2, and ABCC4) in which variation has been suggested to affect the pharmacokinetics of drugs commonly employed to treat HIV/AIDS. We show that genotyping for ABCB1 variations (rs1045642 and rs2032582) may help predict HIV treatment response. We found variations in this gene have a significant association with outcome as measured by CD4+ T cell counts in a discovery subset (N= 197; odds ratio (OR) = 1.58; 95% CI 1.02-2.45), these results were confirmed in a validation subset of the cohort (N = 78; OR= 2.81; 95% CI 1.32-5.96). Exploratory analysis suggests that this effect may be specific to NVP (nevirapine) or 3TC (lamivudine) response. This publication represents the first genetic analysis in a continuing effort to study and assist the patients in a very large, unique, and historically significant HIV-AIDS cohort. Genotyping of AIDS patients for ABCB1 variation may help predict outcome and potentially could help guide treatment strategies.