The associations between metals/metalloids concentrations in blood plasma of Hong Kong residents and their seafood diet, smoking habit, body mass index and age.

The concentrations of metals/metalloids in blood plasma collected from 111 healthy residents (51 female, 60 male) in Hong Kong (obtained from the Hong Kong Red Cross Blood Transfusion Service, from March to April 2008) were quantified by means of a double-focusing sector field inductively coupled plasma optical emission spectrometer (ICP-OES). Results showed that concentrations of these toxic metals such as Hg, Cd, and Pb in Hong Kong residents were not serious when compared with other countries. Males accumulated significantly higher (p < 0.05 or 0.01) Fe (female 0.92 mg/L; male 1.28), Sn (0.44 µg/L; 0.60), Cr (0.77; 0.90), Hg (1.01; 1.73), and Pb (23.4; 31.6) than females. Smokers accumulated significantly higher (p < 0.05) Cd (smoker 0.27 µg/L; nonsmoker 0.17) and Pb (32.8; 17.6) than nonsmokers. Positive correlations were found between concentrations of As, Cd, Pb, and Hg, with respect to seafood diet habit, body mass index (BMI), and age. More intensive studies involving more samples are needed before a more definite conclusion can be drawn, especially on the causal relationships between concentrations of metals/metalloids with dietary preference and lifestyle of the general public.

Sequence variations of full-length hepatitis B virus genomes in Chinese patients with HBsAg-negative hepatitis B infection.

BACKGROUND: The underlying mechanism of HBsAg-negative hepatitis B virus (HBV) infection is notoriously difficult to elucidate because of the extremely low DNA levels which define the condition. We used a highly efficient amplification method to overcome this obstacle and achieved our aim which was to identify specific mutations or sequence variations associated with this entity. METHODS: A total of 185 sera and 60 liver biopsies from HBsAg-negative, HBV DNA-positive subjects or known chronic hepatitis B (CHB) subjects with HBsAg seroclearance were amplified by rolling circle amplification followed by full-length HBV genome sequencing. Eleven HBsAg-positive CHB subjects were included as controls. The effects of pivotal mutations identified on regulatory regions on promoter activities were analyzed. RESULTS: 22 and 11 full-length HBV genomes were amplified from HBsAg-negative and control subjects respectively. HBV genotype C was the dominant strain. A higher mutation frequency was observed in HBsAg-negative subjects than controls, irrespective of genotype. The nucleotide diversity over the entire HBV genome was significantly higher in HBsAg-negative subjects compared with controls (p = 0.008) and compared with 49 reference sequences from CHB patients (p = 0.025). In addition, HBsAg-negative subjects had significantly higher amino acid substitutions in the four viral genes than controls (all p<0.001). Many mutations were uniquely found in HBsAg-negative subjects, including deletions in promoter regions (13.6%), abolishment of pre-S2/S start codon (18.2%), disruption of pre-S2/S mRNA splicing site (4.5%), nucleotide duplications (9.1%), and missense mutations in "α" determinant region, contributing to defects in HBsAg production. CONCLUSIONS: These data suggest an accumulation of multiple mutations constraining viral transcriptional activities contribute to HBsAg-negativity in HBV infection.

Inferring influenza infection attack rate from seroprevalence data.

Seroprevalence survey is the most practical method for accurately estimating infection attack rate (IAR) in an epidemic such as influenza. These studies typically entail selecting an arbitrary titer threshold for seropositivity (e.g. microneutralization [MN] 1∶40) and assuming the probability of seropositivity given infection (infection-seropositivity probability, ISP) is 100% or similar to that among clinical cases. We hypothesize that such conventions are not necessarily robust because different thresholds may result in different IAR estimates and serologic responses of clinical cases may not be representative. To illustrate our hypothesis, we used an age-structured transmission model to fully characterize the transmission dynamics and seroprevalence rises of 2009 influenza pandemic A/H1N1 (pdmH1N1) during its first wave in Hong Kong. We estimated that while 99% of pdmH1N1 infections became MN1∶20 seropositive, only 72%, 62%, 58% and 34% of infections among age 3-12, 13-19, 20-29, 30-59 became MN1∶40 seropositive, which was much lower than the 90%-100% observed among clinical cases. The fitted model was consistent with prevailing consensus on pdmH1N1 transmission characteristics (e.g. initial reproductive number of 1.28 and mean generation time of 2.4 days which were within the consensus range), hence our ISP estimates were consistent with the transmission dynamics and temporal buildup of population-level immunity. IAR estimates in influenza seroprevalence studies are sensitive to seropositivity thresholds and ISP adjustments which in current practice are mostly chosen based on conventions instead of systematic criteria. Our results thus highlighted the need for reexamining conventional practice to develop standards for analyzing influenza serologic data (e.g. real-time assessment of bias in ISP adjustments by evaluating the consistency of IAR across multiple thresholds and with mixture models), especially in the context of pandemics when robustness and comparability of IAR estimates are most needed for informing situational awareness and risk assessment. The same principles are broadly applicable for seroprevalence studies of other infectious disease outbreaks.

Donors' perspectives on self-deferral of men having sex with men from blood donation.

BACKGROUND: Self-deferral of men having sex with men (MSM) from blood donation is a means of protecting blood safety. There has recently been a strategy change from permanent to time-limited deferral in some countries. Awareness and attitudes of donors is crucial for effective implementation of MSM deferral or any change of the strategy. STUDY DESIGN AND METHODS: A postdonation survey was administered using a Web-based questionnaire, after explanation by trained volunteers, to evaluate donors' awareness and compliance toward the health history enquiry (HHE, the deferral questionnaire) of the Hong Kong Red Cross Blood Transfusion Service, sexual experiences, and opinions on permanent versus time-limited deferral. RESULTS: A total of 1373 Chinese donors (male:female 1.28:1), a majority (89.1%) of whom were repeat donors, completed the survey at eight blood donation centers. Almost all (98.7%) were aware of HHE, although only half read it in detail, the latter comprising more experienced donors. Most did not hold strong views on deferral, with more than half (59.4%) concurring with both permanent and time-limited deferral. Seventeen (3.2%) of the sexually active male donors were MSM, of whom six disagreed with permanent deferral while seven agreed with changing to time-limited deferral. A simpler question structure was preferred by 57% of the respondents for screening MSM to achieve self-deferral. CONCLUSIONS: Donors generally do not read through the deferral questionnaire in sufficient detail for making an informed decision. Blood safety would eventually depend on donors' compliance with the deferral mechanism, irrespective of whether it is permanent or time-limited.

Role of HLA-DP polymorphisms on chronicity and disease activity of hepatitis B infection in Southern Chinese.

BACKGROUND AND AIMS: The association between HLA-DP single nucleotide polymorphisms (SNPs) and chronic hepatitis B virus (HBV) infection varies between different populations. We aimed to study the association between HLA-DP SNPs and HBV infection and disease activity in the Chinese population of Hong Kong. METHODS: We genotyped SNPs rs3077 (near HLA-DPA1) and rs9277378 and rs3128917 (both near HLA-DPB1) in 500 HBV carriers (hepatitis B surface antigen [HBsAg]-positive), 245 non-HBV infected controls (HBsAg- and antibody to hepatitis B core protein [anti-HBc]-negative), and 259 subjects with natural HBV clearance (HBsAg-negative, anti-HBc-positive). Inactive HBV carriers state was defined by HBV DNA levels <2,000 IU/ml and persistently normal alanine aminotransferase level for least 12 months. RESULTS: Compared to the non-HBV infected subjects, the HBV carriers had a significantly lower frequency of the rs3077 T allele (p = 0.0040), rs9277378 A allele (p = 0.0068) and a trend for lower frequency of rs3128917 T allele (p = 0.054). These alleles were associated with an increased chance of HBV clearance (rs3077: OR = 1.41, p = 0.0083; rs9277378: OR = 1.61, p = 0.00011; rs3128917: OR = 1.54, p = 0.00017). Significant associations between HLA-DP genotypes and HBV clearance were also found under different genetic models. Haplotype TAT was associated with an increased chance of HBV clearance (OR = 1.64, p = 0.0013). No association was found between these SNPs and HBV disease activity. CONCLUSION: HLA-DP SNPs rs3077, rs9277378 and rs3128917 were associated with chronicity of HBV disease in the Chinese. Further studies are required to determine whether these SNPs influence the disease endemicity in different ethnic populations.

Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection.

BACKGROUND: Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking. METHODS: This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-IVIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-IVIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared. RESULTS: Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-IVIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04). CONCLUSIONS: Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality. TRIAL REGISTRY: ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.

Enhanced detection of hepatitis B virus in Hong Kong blood donors after introduction of a more sensitive transcription-mediated amplification assay.

BACKGROUND: A total of 517,072 and 399,326 consecutive donations were screened for hepatitis B virus (HBV) by individual-donation nucleic acid testing (ID-NAT) using Ultrio and Ultrio Plus assays (Novartis Diagnostics), respectively. The impact of more sensitive HBV detection by the latter assay version was established by comparing NAT yield and transmission risk. STUDY DESIGN AND METHODS: Donations were screened simultaneously for HBV serologic markers and ID-NAT, followed by discriminatory assay and confirmatory test algorithms. Window period (WP) reduction and residual HBV transmission risk were computed using mathematical modeling. RESULTS: HBV NAT-yield rates for both WP and occult HBV infection (OBI) increased significantly from 1:34,471 to 1:17,362 (p = 0.036) and from 1:5120 to 1:2450 (p < 0.0001), despite a 1.2- and 1.6-fold decrease in hepatitis B surface antigen (HBsAg) incidence and prevalence rates respectively. After adjusting for this bias, the WP and OBI NAT-yield improvement factors were 2.3 and 3.4, respectively, higher than a less than 1.5-fold increase estimated from analytical sensitivity studies on HBV Genotype A and C standards. The current WP transmission risk with Ultrio Plus screening was estimated at 1:55,000 compared to 1:22,000 with HBsAg testing. CONCLUSION: The observed greater than twofold enhanced WP NAT yield with the Ultrio Plus assay can be explained by greater than 10-fold increased analytical sensitivity in detecting the HBV Genotype B and C strains in Hong Kong. Direct comparison studies of the two assay versions on dilutions of HBV NAT-yield samples are required to confirm this hypothesis.

Estimating infection attack rates and severity in real time during an influenza pandemic: analysis of serial cross-sectional serologic surveillance data.

BACKGROUND: In an emerging influenza pandemic, estimating severity (the probability of a severe outcome, such as hospitalization, if infected) is a public health priority. As many influenza infections are subclinical, sero-surveillance is needed to allow reliable real-time estimates of infection attack rate (IAR) and severity. METHODS AND FINDINGS: We tested 14,766 sera collected during the first wave of the 2009 pandemic in Hong Kong using viral microneutralization. We estimated IAR and infection-hospitalization probability (IHP) from the serial cross-sectional serologic data and hospitalization data. Had our serologic data been available weekly in real time, we would have obtained reliable IHP estimates 1 wk after, 1-2 wk before, and 3 wk after epidemic peak for individuals aged 5-14 y, 15-29 y, and 30-59 y. The ratio of IAR to pre-existing seroprevalence, which decreased with age, was a major determinant for the timeliness of reliable estimates. If we began sero-surveillance 3 wk after community transmission was confirmed, with 150, 350, and 500 specimens per week for individuals aged 5-14 y, 15-19 y, and 20-29 y, respectively, we would have obtained reliable IHP estimates for these age groups 4 wk before the peak. For 30-59 y olds, even 800 specimens per week would not have generated reliable estimates until the peak because the ratio of IAR to pre-existing seroprevalence for this age group was low. The performance of serial cross-sectional sero-surveillance substantially deteriorates if test specificity is not near 100% or pre-existing seroprevalence is not near zero. These potential limitations could be mitigated by choosing a higher titer cutoff for seropositivity. If the epidemic doubling time is longer than 6 d, then serial cross-sectional sero-surveillance with 300 specimens per week would yield reliable estimates when IAR reaches around 6%-10%. CONCLUSIONS: Serial cross-sectional serologic data together with clinical surveillance data can allow reliable real-time estimates of IAR and severity in an emerging pandemic. Sero-surveillance for pandemics should be considered.

Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection.

BACKGROUND: Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. METHODS: During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥ 1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. RESULTS: Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio [OR], .20; 95% confidence interval [CI], .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. CONCLUSIONS: Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

Transmissibility of hepatitis B virus (HBV) infection through blood transfusion from blood donors with occult HBV infection.

BACKGROUND: Studies of the transmissibility of hepatitis B virus (HBV) in occult hepatitis B (OHB) through blood transfusion are scarce. We aimed to determine the transmissibility of HBV in blood donors with OHB through transfusion in animal and human studies. METHODS: Among 217,595 blood donors, 67 donors with OHB were identified. Four chimeric mice populated with human hepatocytes were inoculated with 2 donor serum samples. Serial serum and liver HBV DNA levels were measured. Forty-nine recipients of blood transfusions traced from 10 donors with OHB (9 of whom were positive for antibody to hepatitis B surface antigen [anti-HBs]) were tested for HBV infection. Homology and phylogenetic analyses between the HBV genomic sequences of donors and recipients were performed. RESULTS: Serum HBV DNA was detectable (10(4) copies/mL) in 1 mouse at weeks 5 and 7 after inoculation. Total HBV DNA and HBV replication template (covalently closed circular DNA) and hepatitis B core antigen were detected in the mouse liver. After transfusion, 45 recipients (91.8%) had no HBV infection (ie, they tested negative for hepatitis B surface antigen and HBV DNA). Four tested positive for HBV DNA. In 3 recipients, 83%-86% homology and distant phylogenetic relatedness with their donor HBV excluded transmission through transfusion. The remaining recipient HBV had 95% sequence homology with her donor HBV, compatible with acquisition of HBV infection from the transfusion. High anti-HBs levels in 7 other recipients suggested recent transfusion-related HBV immune response. CONCLUSIONS: OHB donor blood infectivity was shown in our animal and human studies. However, the risk of HBV transmission in humans was low, especially from blood products obtained from donors with OHB who were anti-HBs positive.

The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong.

BACKGROUND: Serial cross-sectional data on antibody levels to the 2009 pandemic H1N1 influenza A virus from a population can be used to estimate the infection attack rates and immunity against future infection in the community. METHODS: From April through December 2009, we obtained 12,217 serum specimens from blood donors (aged 16-59 years), 2520 specimens from hospital outpatients (aged 5-59 years), and 917 specimens from subjects involved in a community pediatric cohort study (aged 5-14 years). We estimated infection attack rates by comparing the proportions of specimens with antibody titers ≥ 1:40 by viral microneutralization before and after the first wave of the pandemic. Estimates were validated using paired serum samples from 324 individuals that spanned the first wave. Combining these estimates with epidemiologic surveillance data, we calculated the proportion of infections that led to hospitalization, admission to the intensive care unit (ICU), and death. RESULTS: We found that 3.3% and 14% of persons aged 5-59 years had antibody titers ≥ 1:40 before and after the first wave, respectively. The overall attack rate was 10.7%, with age stratification as follows: 43.4% in persons aged 5-14 years, 15.8% in persons aged 15-19 years, 11.8% in persons aged 20-29 years, and 4%-4.6% in persons aged 30-59 years. Case-hospitalization rates were 0.47%-0.87% among persons aged 5-59 years. Case-ICU rates were 7.9 cases per 100,000 infections in persons aged 5-14 years and 75 cases per 100,000 infections in persons aged 50-59 years, respectively. Case-fatality rates were 0.4 cases per 100,000 infections in persons aged 5-14 years and 26.5 cases per 100,000 infections in persons aged 50-59 years, respectively. CONCLUSIONS: Almost half of all school-aged children in Hong Kong were infected during the first wave. Compared with school children aged 5-14 years, older adults aged 50-59 years had 9.5 and 66 times higher risks of ICU admission and death if infected, respectively.

Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: a study of a large blood donor population.

BACKGROUND AND AIMS: The aim of the present study was to determine the population prevalence of occult hepatitis B (OHB) infection and its clinical profile in a highly endemic area of chronic hepatitis B virus disease. METHODS: OHB was first identified by individual sample testing for hepatitis B surface antigen (HBsAg) followed by nucleic acid testing (NAT) and vice versa for 3044 (cohort 1, stored sera from donation within 1 year) and 9990 (cohort 2, prospective study) blood donors, respectively. OHB was confirmed meticulously by ≥2 out of 3 tests with detectable hepatitis B virus (HBV) DNA using a sensitive standardised assay. Detailed serology and viral load in the serum and liver were studied. RESULTS: The prevalence of OHB was 0.13% (4/3044) and 0.11% (11/9967) for cohort 1 and 2, respectively. In cohort 2, 10 out of 11 OHB samples were positive for anti-HBc (hepatitis B core antigen) antibody (all were immunoglobulin G). Seven had detectable anti-HBs. The serum HBV DNA levels were extremely low (highest 14.1 IU/ml). Of the six donors who underwent liver biopsies, all had normal liver biochemistry, extremely low liver HBV DNA (highest 6.21 copies/cell) and nearly normal liver histology. For those with viral sequence generation, none had the common HBsAg mutant G145R. CONCLUSIONS: The prevalence of OHB in a highly endemic area of chronic HBV was very low, thus implying a low impact on transfusion services. To implement universal screening, the high cost of NAT should be taken into account. OHB blood donors had very low HBV replication, and normal liver biochemistry and histology, conferring a favourable prognosis.

The genetic variability of MDR1 C3435T polymorphisms in four Southern Chinese populations.

OBJECTIVES: To investigate the genetic variability of multiple drug resistant 1 (MDR1) gene C3435T polymorphism in four Southern Chinese populations. METHODS: Using discrimination real-time PCR, we determined the MDR1 C3435T polymorphism in three ethnic minority groups Lahu (n=104), Wa (n=101) and Bulang (n=100) in Yunnan Province, and Han Chinese (n=199) in Hong Kong. All of them were residents in Southern China. RESULTS: For 3435 CC genotype, the frequency in Han Chinese in Hong Kong (44.7%) is significantly higher than in Lahu (16.3%) and Wa (29.7%) minorities, P<0.05. For 3435 CT genotype, the frequency in Han Chinese in Hong Kong (44.2%) is lower than in Lahu (58.7%), P<0.05. For 3435 TT genotype, frequency in Han Chinese in Hong Kong (11.1%) is lower than in Lahu (25%) and Wa (20.8%), P<0.05. For 3435 C allele, frequency in Han Chinese in Hong Kong (66.8%) is higher than in Lahu (45.7%) and Wa (54.5%), P<0.01. For 3435T allele, frequency in Han Chinese in Hong Kong (33.2%) is lower than in Lahu (54.3%) and Wa (45.5%), P<0.01. For MDR1 3435T allele, the frequencies are significantly higher in our four Southern Chinese populations than in African population (P<0.001) and significantly lower than in South-west Asians (P<0.05); Han Chinese in Hong Kong displayed significant difference from all the other ethnic populations except Japanese (P<0.05); compared with Caucasian and other ethnic Asians, Lahu minority showed no frequency difference (P>0.05) between Caucasian and other Asians (except Japanese). CONCLUSIONS: This is the first study to show the C3435T polymorphism of MDR1 in Southern Chinese populations. The frequency of C3435T, an important determinant for multidrug resistance, displays significant difference in ethnics. It may help for individualizing therapy for cancer, HIV and other common diseases.

Genetic variability of CYP2B6 polymorphisms in four southern Chinese populations.

AIM: To investigate the genotype and allelic frequencies of Cytochrome P450 2B6 polymorphisms in four southern Chinese populations. METHODS: DNA was obtained from blood samples from Han Chinese from Hong Kong and three minority groups, the Wa, Bulang and Lahu from Yunnan in southern China. Genotyping was performed using real-time PCR and confirmed by direct sequencing. RESULTS: A total of 507 subjects from southern China were studied. Results showed there is a high prevalence of 516G > T (34.5%) in ethnic Chinese compared to literature reports on other Asian populations and Caucasians. The frequency of the 516TT genotype is higher in the Han majority (23.1%) than in three other ethnic minority groups (i.e., 7.4%, 9.1% and 15.8%) in southern China. CONCLUSION: This was the first study to document the spectrum of CYP2B6 allelic variants and genotypes in a southern Chinese population. The 516G > T allele is associated with a defective metabolism of efavirenz (EFV), which therefore may predispose to drug toxicity. Treatment regimens for human immunodeficiency virus (HIV) and heroin addiction may need to be optimized in different populations because of the marked variability of the key metabolizing enzyme.

Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study.

BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age < or =65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group.

HLA-B alleles, high-risk HPV infection and risk for cervical neoplasia in southern Chinese women.

A population-based study was conducted on 256 southern Chinese with cervical intraepithelial neoplasia grade III (CIN III) or invasive cervical cancer (ICC) and on 258 controls to examine the associations between HLA-B alleles, infection with high-risk human papillomaviruses (HPVs) and the development of cervical neoplasia. HLA-B15 was found to be protective for CIN III/ICC overall (p(corrected) = 0.003), and for HPV52-positive CIN III/ICC (p(corrected) = 0.003). A marginal protective effect of B15 was observed for HPV16-positive CIN III/ICC, but no significant associations were revealed for HPV18- or HPV58-positive cases. None of the HLA-B alleles were found to confer an increased risk for cervical neoplasia. HLA-B15 is common among Asian for whom HPV52, a worldwide uncommon HPV type, also exists in a relatively high prevalence. It would also be worthwhile to assess the association between HLA-B15, HPV52 and cervical cancer in other Asian populations.

Carrier incidence for spinal muscular atrophy in southern Chinese.

A real time quantitative PCR (QPCR) method using TaqMan technology was used to assess the copy number of the two survival motor neuron genes (SMN1 and SMN2) on chromosome 5q13. This allows the accurate determination of carriers for spinal muscular atrophy (SMA), with one copy of SMN1. Analysis of 569 normal southern Chinese individuals revealed a carrier incidence of 1.6%, similar to that found in the western society. Study of 42 obligatory carriers showed a (2 + 0) genotype in two (4.8 %). In 27 SMA patients with homozygous deletion of the SMN1 gene, the number of SMN2 gene correlated with disease phenotype, with 68% of type II and III patients carrying three or more SMN2 genes, whilst the incidence of three or more SMN2 genes in the normal population was 1.57%.