HLA and Disease: Relative-Risk Regression Methods and Multiple Testing Considerations

Rl, Prentice; Storb, Rainer; Ks, Brown; Mw, Mason

doi:10.2307/2530908

Cited by 15 publications

(6 citation statements)

References 12 publications

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“…To address the multiplicity of alleles at each locus, we performed overall tests of association for these A, B, and C loci alleles. 24,25 The overall test was also performed using all alleles expressed at these three loci regardless of frequency of expression within our cohort. P values based on the likelihood ratio test represent the probability that at least one allele in the specific locus is significantly associated with incident infant HIV-1 infection.…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen (HLA) B*18 and Protection against Mother-to-Child HIV Type 1 Transmission

Farquhar

Rowland‐Jones²,

Mbori‐Ngacha³

et al. 2004

AIDS Research and Human Retroviruses

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Human leukocyte antigen (HLA) molecules regulate the cellular immune system and may be determinants of infant susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. Molecular HLA typing for class I alleles was performed on infants followed in a Kenyan perinatal cohort. Early HIV-1 infection status was defined as infection occurring at birth or month 1, while late infection via breast milk was defined as first detection of HIV-1 after 1 month of age. Likelihood ratio tests based on a proportional hazards model adjusting for maternal CD4 T cell count and HIV-1 viral load at 32 weeks of gestation were used to test associations between infant allelic variation and incident HIV-1 infection. Among 433 infants, 76 (18%) were HIV-1 infected during 12 months of follow-up. HLA B*18 was associated with a significantly lower risk of early HIV-1 transmission [relative risk (RR) = 0.26; 95% confidence interval (CI) 0.04-0.82], and none of the 24 breastfeeding infants expressing HLA B*18 who were uninfected at month 1 acquired HIV-1 late via breast milk. We observed a trend toward increased early HIV-1 acquisition for infants presenting HLA A*29 (RR = 2.0; 95% CI 1.0-3.8) and increased late HIV-1 acquisition via breast milk for both Cw*07 and Cw*08 (RR = 4.0; 95% CI 1.0-17.8 and RR = 7.2; 95% CI 1.2-37.3, respectively). HLA B*18 may protect breast-feeding infants against both early and late HIV-1 acquisition, a finding that could have implications for the design and monitoring of HIV-1 vaccines targeting cellular immune responses against HIV-1.

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Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigen (HLA) B*18 and Protection against Mother-to-Child HIV Type 1 Transmission

Farquhar

Rowland‐Jones²,

Mbori‐Ngacha³

et al. 2004

AIDS Research and Human Retroviruses

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“…Comparison of antigen frequencies between leprosy patients and healthy controls was made using a simple chi-square comparison test. For each locus a multivariate binary logistic regression model was used to test a global hypothesis of association between the distribution of alleles and risk of disease (Cox 1970, Prentice 1976, Prentice et al 1984. Only alleles with an occurrence of ten or more cases were included as covariates in the regression models.…”

Section: Discussionmentioning

confidence: 99%

HLA and leprosy in Koreans

et al. 1987

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HLA antigens in 157 unrelated Koreans with leprosy have been identified and compared with 162 healthy Korean controls. The patient group consisted of 124 with lepromatous leprosy and 33 with tuberculoid leprosy. Although no significant differences were detected between the two patient groups, several antigens were found to be increased in the combined patient group compared to healthy controls. Two Class I antigens were increased: HLA-All (22% vs 12%) and Aw33 (27% vs 14%). Four Class I1 antigens were increased: HLA-DR1 (16% vs 7%), DR2 (39% vs 21%). DRw9 (14% vs 6%) and DQwl (74% vs 55%). HLA-DR4 (28% vs a%), DRw53 (46% vs 69%) and DQw3 (500/, vs 75%) in contrast were significantly decreased in patients. Interaction of DRI, DR2, DRw9 and DQwl as risk factors was analyzed. HLA-DR2 appeared to be the strongest risk factor. N o evidence for synergy between DRI. DR2 and DRw9 was detected. DQwl was not significantly increased in patients in the absence of DRl and DR2, and thus it was not apparent in this study that DQwl was an independent risk factor.

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“…The multivariate Cox proportional-hazards model [Cox, 1972] was used to develop an overall test of the hypothesis that HLA antigens are unrelated to AIDS [Prentice et al, 1984] and to produce estimated relative-risk factors corresponding to the presence of each particular allele or haplotype on one or both chromosomes, while adjusting for any confounding variable. This approach to the problem of HLA and AIDS association takes detailed account of times to disease occurrence or censorship for a particular al lele, censoring being due either to loss to follow-up or to no-AIDS status at the end of the study period.…”

Section: Methodsmentioning

confidence: 99%

HLA-Associated Susceptibility to Acquired Immune Deficiency Syndrome in HIV-1-Seropositive Subjects

Kaplan

Muller²,

Doînel

et al. 1990

Hum Hered

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No difference in HLA-A, B or DR gene frequencies could be observed between 172 control subjects and 180 HIV-1-seropositive subjects of European ancestry diagnosed through the systematic screening of blood donations. In contrast, progression to acquired immune deficiency syndrome (AIDS; 21 patients) or CD4 lymphocyte loss equal or more than 20% over a 6-month period (37 subjects) was found to be associated with the B8DR3 haplotype (relative risk = 10.64, p < 0.003, and 2.23, p < 0.092, respectively). Other independently significant associations assessed through the multivariate Cox proportional-hazards model were B16, BW21 and B35 alleles as factors of bad prognosis. Conversely, A1 and DR4 alleles were factors favouring longer survival.

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HLA and Disease: Relative-Risk Regression Methods and Multiple Testing Considerations

Cited by 15 publications

References 12 publications

Human Leukocyte Antigen (HLA) B*18 and Protection against Mother-to-Child HIV Type 1 Transmission

Human Leukocyte Antigen (HLA) B*18 and Protection against Mother-to-Child HIV Type 1 Transmission

HLA and leprosy in Koreans

HLA-Associated Susceptibility to Acquired Immune Deficiency Syndrome in HIV-1-Seropositive Subjects

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