KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians.

BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation. HBV is highly prevalent in The Gambia and the commonest cause of liver disease. The Gambia Liver Cancer Study was a matched case-control study conducted between September 1997 and January 2001 where cases with liver disease were identified in three tertiary referral hospitals and matched with out-patient controls with no clinical evidence of liver disease. METHODS: We typed 15 KIR genes using the polymerase chain reaction with sequence specific primers (PCR-SSP) in 279 adult Gambians, 136 with liver disease (HCC or Cirrhosis) and 143 matched controls. We investigated effects of KIR genotypes and haplotypes on HBV infection and associations with cirrhosis and HCC. RESULTS: Homozygosity for KIR group A gene-content haplotype was associated with HBsAg carriage (OR 3.7, 95% CI 1.4-10.0) whilst telomeric A genotype (t-AA) was associated with reduced risk of e antigenaemia (OR 0.2, 95% CI 0.0-0.6) and lower viral loads (mean log viral load 5.2 vs. 6.9, pc = 0.022). One novel telomeric B genotype (t-ABx2) containing KIR3DS1 (which is rare in West Africa) was also linked to e antigenaemia (OR 8.8, 95% CI 1.3-60.5). There were no associations with cirrhosis or HCC. CONCLUSION: Certain KIR profiles may promote clearance of hepatitis B surface antigen whilst others predispose to e antigen carriage and high viral load. Larger studies are necessary to quantify the effects of individual KIR genes, haplotypes and KIR/HLA combinations on long-term viral carriage and risk of liver cancer. KIR status could potentially inform antiviral therapy and identify those at increased risk of complications for enhanced surveillance

Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures

Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. Exome sequencing data were used to identify rare variants in known genes in CHH ( <i>n</i>  = 116), CDGP ( <i>n</i>  = 72) and control cohorts ( <i>n</i>  = 36 874 ExAC and <i>n</i>  = 405 CoLaus). Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, <i>P</i>  = 7.6 × 10 <sup>-11</sup> ) or controls (18%, <i>P</i>  = 5.5 × 10 <sup>-12</sup> ). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, <i>P</i>  = 0.002) and controls (2%, <i>P</i>  = 6.4 × 10 <sup>-7</sup> ). Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty

Tolerancing and characterization of curved image sensor systems

International audienceCurved image sensors, not having to correct the field curvature, are considered a relevant solution for improving the vast majority of optical systems. They offer the possibility of designing compact aberration-free optical systems. In this work, we explain the advantage of the curved sensor system using the aberration theory. A complete procedure was developed to produce functional curved sensors and functional prototypes were carried out. This paper focuses on the tolerancing process of curved sensors and its inclusion in optical design. A compact objective prototype designed and produced demonstrates the advantage of curvature and the impact of tolerancing

The genomic organisation of <i>KIR</i> genes on human chromosome 19.

<p><i>KIR</i> genes are tightly organised head-to-tail over approximately 150 kb within the Leukocyte Receptor Complex (LRC). Inhibitory <i>KIR</i> genes are shown in green, activating genes in orange, pseudogenes in yellow, and the recombination hotspot in black. <i>KIR</i> genes vary in size ranging from 10 kb to 16 kb and are separated from each other by about 2 kb of intergenic space, except for the 14 kb recombination hotspot zone upstream of <i>KIR2DL4</i> that separates telomeric from centromeric KIRs.</p

<i>KIR</i> genotypes and outcomes of hepatitis B infection.

<p><i>KIR</i> genotypes and outcomes of hepatitis B infection.</p

Centromeric and telomeric genotype distribution.

<p>a) Genomic organisation of centromeric genotypes present in at least 2% of the study population, b) <i>KIR</i> genes present telomeric genotypes (those found in at least 2% of the study population). Filled box: gene is present; open box: gene is absent, x: known or novel motifs (e.g. Bx2: second novel B motif identified for the first time in this study), N: number of individuals carrying the genotype of interest.</p

Characteristics of study participants.

<p>Characteristics of study participants.</p