Predictors of the rate of change in disease activity over time in LUMINA, a multiethnic US cohort of patients with systemic lupus erythematosus: LUMINA LXX.

The objectives of the present study were (1) to clarify and quantify the relationship between age and disease duration with the rate of change in disease activity over time in patients with systemic lupus erythematosus (SLE) and (2) to explore other possible factors associated with this rate of change. To this end, SLE patients from LUMINA were studied if they had at least three visits in which disease activity (Systemic Lupus Activity Measure-Revised [SLAM-R]) had been ascertained. Variables associated with the rate (slope) of change in disease activity (obtained by regressing the SLAM-R score against the length of time from diagnosis to visit date) were examined by univariable and multivariable analyses. Five hundred and forty two of the 632 patients had at least three SLAM-R score. In multivariable analyses, Whites exhibited the fastest decline in disease activity, Texan Hispanics exhibited the slowest, trailed by the African Americans. Longer disease duration and HLA-DRB1*1503 positivity were associated with a slower decline whereas a greater number of American College of Rheumatology criteria and abnormal laboratory parameters (white blood cell counts, hematocrit and serum creatinine) were associated with a faster decline. These findings complement existing knowledge on SLE disease activity and are potentially useful to clinicians managing these patients.

Epidemiology of IDDM in black and white children in Jefferson County, Alabama, 1979-1985.

For the period of 1 January 1979 through 31 December 1985, an average annual incidence rate (IR) of 12.1/100,000 (95% confidence interval [10.4/100,000, 14.0/100,000]) of insulin-dependent diabetes mellitus (IDDM) was observed in Jefferson County, Alabama, among people less than 20 yr old. Hospital medical-record review was the primary source of case ascertainment. A large proportion of Black children in the county permitted race-specific analyses. The average annual IR among the Black children was less than half that observed in the White children (7.0/100,000 vs. 15.6/100,000, respectively). Nearly equal numbers of White boys and girls were diagnosed during this period; however, there were three times as many Black girls as Black boys diagnosed. Among the 134 Whites, age-specific annual IRs were highest in the 5- to 9- and 10- to 14-yr age groups. Little variation was observed in age-specific rates among the 41 Black subjects. A seasonal trend was evident in both races, with the fewest cases of IDDM diagnosed in the months of April through June (P less than .001). No association between the incidence of diabetes and income level was found among White or Black children. Significant differences in the epidemiology of IDDM between White and Black children suggest an important avenue for studying the etiology of IDDM.

HLA-A, -B, and -DR associations in type I diabetes mellitus with onset after age forty.

It remains to be convincingly demonstrated whether insulin-requiring, ketosis-prone, lean-at-onset, type I diabetics who develop their disease after age 40 have the same disease as the children with similar characteristics. To address this question, we examined the population HLA genetic associations of this group. One hundred forty white, insulin-using diabetics with onset of disease past age 40 yr and 268 normal white controls have thus far been analyzed for HLA type. In the group of patients who were lean-at-onset and/or ketosis-prone (N = 54), there was a significantly increased frequency of DR4 (RR = 4.63; P less than 0.01) and significantly decreased frequency of DR2 (RR = 0.18; P less than 0.05) after correction. DR4 was also significantly increased after correction (RR = 5.72; P less than 0.25) in the subgroup who were both lean and ketosis-prone (N = 23). No significant differences in HLA-DR frequencies were found between the obese and not-ketosis-prone group (N = 69) and controls. No significant associations of HLA-A or-B antigens with either group were observed after correction for the number of antigens tested. To our knowledge, this is the first such study in the United States, and the first demonstrating that late onset diabetics who are lean-at-onset and/or ketosis-prone exhibit HLA-DR antigen associations which are similar to early onset cases.

Evidence for genetic admixture as a determinant in the occurrence of insulin-dependent diabetes mellitus in U.S. blacks.

In recent years, it has been proposed that genetic admixture may have played a role in the increased frequency of insulin-dependent diabetes mellitus (IDDM) in young U.S. blacks relative to African blacks. In support of this proposal, the similar associations of specific markers of the major histocompatibility complex (MHC) with IDDM in U.S. blacks with respect to U.S. whites have been cited. To determine whether racial admixture was a factor in the increased prevalence, we did three analyses of admixture. In the first we used nine genetic markers (ABO, Rh, Fy, Hp, Gc, Pl, OR, Tfr, and Gm) and determined that there was significantly greater than zero genetic contribution from whites in our sample of U.S. black IDDM patients (9.6 +/- 2.3%, P less than 0.01) when a sample of U.S. blacks without IDDM was used as one "parental" population. In the next two analyses, we estimated the amounts of genetic contribution from whites in the U.S. blacks with and without IDDM using reported gene frequencies for West African blacks for four genetic markers (ABO, Rh, Fy, and Hp). The estimate of admixture (21.4 +/- 2.8%) for the black IDDM sample was greater than that for the U.S. black controls (17.9 +/- 2.3%), although the difference was not significant. Our estimate of genetic contribution from whites, 21.4% for black IDDM patients, supports the assumptions of 20% admixture which MacDonald and Rotter and Hodge used to test their respective models for the inheritance of IDDM. These results support the hypothesis that admixture with the white population is, in part, responsible for the increase in prevalence of IDDM seen in U.S. blacks.

Epidemiology of childhood IDDM in U.S. Virgin Islands from 1979 to 1988. Evidence of an epidemic in early 1980s and variation by degree of racial admixture.

OBJECTIVE: The epidemiology of insulin-dependent diabetes mellitus (IDDM) was evaluated in a predominantly black population in the U.S. Virgin Islands. RESEARCH DESIGN AND METHODS: Primary ascertainment of diabetic subjects was by retrospective review of hospital and clinic records, and IDDM was defined by Diabetes Epidemiology Research International Group criteria. RESULTS: For the period 1979-1988, 28 children less than 15 yr of age were diagnosed with IDDM resulting in an average annual IDDM incidence rate (IR) of 7.5/100,000 (95% confidence interval 4.7-10.3). A significant increase in IDDM incidence (P less than 0.01) was observed when the IR rose to 28.4/100,000 in 1984. White children had the highest IR (28.9/100,000). The IR for Hispanics (7.2/100,000) was slightly higher than that for blacks (5.9/100,000). Among black children, a slight but nonsignificant male excess in incidence was observed (male-female ratio 1.5). When black or Hispanic patients were compared with age-matched control subjects with respect to grandparental race, the diabetic subjects had a greater percentage of white ancestry (P less than 0.02 and P less than 0.05, respectively). The incidence of IDDM in Caribbean blacks (West Indians) in the U.S. Virgin Islands was similar to blacks in the U.S. CONCLUSIONS: The epidemic of IDDM in 1984 provides support for a possible pandemic in the early 1980s.

Diabetes and automobile crashes in the elderly. A population-based case-control study.

OBJECTIVE: The aim of this study was to estimate the association between diabetes and its complications and at-fault automobile crashes among older drivers. RESEARCH DESIGN AND METHODS: This was a population-based case-control study. Case subjects were drivers aged > or = 65 years who had been involved in a crash during 1996 in which they were at fault. Two control groups were selected: 1) crash-involved not-at-fault subjects and 2) non-crash-involved subjects. Telephone interviewers collected information on demographic characteristics, driving habits, diabetes sequelae and treatment, other chronic medical conditions, and visual function. RESULTS: Overall, there was no association between diabetes and at-fault crash involvement. The adjusted odds ratio (OR) for diabetes was 1.1 (CI 0.7-1.9) when case subjects were compared with either control group. However, the adjusted OR for diabetes was 2.5 (0.9-7.2) among subjects who had been involved in a crash in the 4 years preceding 1996, while it was only 0.9 (0.5-1.7) among those who had not. There was no evidence of an association between treatment modalities and at-fault crash involvement. Case subjects were, although not significantly (P = 0.25), more likely (OR 2.4) to report neuropathy compared with both control groups, and retinopathy was not associated with increased crash risk. CONCLUSIONS: This study provides no evidence that older drivers with diabetes are at increased risk for automobile crashes. There remains the possibility that those with diabetes who have more severe disease or have had multiple crashes are at increased risk.

Prevalence and risk factors of microalbuminuria in a cohort of African-American women with gestational diabetes.

OBJECTIVE: To study the prevalence of microalbuminuria (MA) in African-American women with a history of gestational diabetes (GDM) who are at high risk for insulin resistance and renal dysfunction and to study MA's relation to insulin resistance, type 2 diabetes, and hypertension. RESEARCH DESIGN AND METHODS: MA was assessed using 24-h, timed, and/or random urine samples in a cross-sectional sample (n = 289) from a cohort of African-American women with a history of GDM and followed for a median of 11 years (range 3.0-18.4) since their diabetic pregnancy. Subjects with a urine albumin excretion rate of 30-300 g/24 h or 30-300 microg/mg creatinine in a random sample were classified as having MA if two of three samples over a 3- to 6-month period were positive. These women were evaluated for family history of diabetes, smoking and alcohol use, BMI, diabetes, hypertension, and lipid abnormalities. Insulin sensitivity was determined using the homeostasis model assessment (HOMA) estimates, which used fasting insulin and glucose measurements obtained at the same time as the MA urine sample. RESULTS: At MA assessment, the women ranged in age from 22 to 57 years, with a median of 39 years. The overall prevalence of MA was 20%; 36% in those with diabetes. Those women with MA had higher rates of diabetes (63.8 vs. 28.6%, odds ratio [OR] = 4.4, P < 0.05), hypertension (82.8 vs. 42.9%, OR = 6.4, P < 0.05), and family history of diabetes (85.7 vs. 61.7%, OR = 3.7, P < 0.05). The proportion of subjects with MA with a family history of hypertension was nonsignificantly increased (92.9 vs. 82.4%). Subjects with MA were more obese (BMI 37.2 +/- 8.9 vs. 34.4 +/- 8.6 kg/m(2)) and had higher levels of HbA(1c) (8.8 +/- 3.3 vs. 6.6 +/- 1.8%, P < 0.001) and systolic (144.3 +/- 25.9 vs. 122.8 +/- 17.2 mmHg, P < 0.0001) and diastolic (95.1 +/- 15.4 vs. 82.5 +/- 11.9 mmHg, P < 0.0001) blood pressures. Lipid fractions were similar in those with and without MA. Although fasting glucose was much higher in subjects with MA (10.3 +/- 5.8 vs. 7.1 +/- 4.2 mmol/l, P = 0.0002), insulin levels were not significantly higher in subjects with MA (17.4 +/- 21.2 vs. 15.2 +/- 12.4 pmol/l). Insulin sensitivity, as measured using log HOMA, was similar (1.5 +/- 0.6 vs. 1.6 +/- 0.6) in women with and without MA, respectively. Multivariable logistic regression analyses indicated that HbA(1c), OR = 1.16 (1.07, 1.27), and systolic blood pressure, OR = 1.27 (1.14, 1.41), were independent risk factors for MA. In those with diabetes, the subjects with MA had higher rates of hypertension-83.8 vs. 56.1%, OR = 4.1 (1.5, 11.10)-which was reflected by their higher systolic and diastolic blood pressures, 146.1 mmHg (P = 0.001) and 94.8 mmHg (P = 0.002), respectively, and lower levels of VLDL (0.45 +/- 0.22 vs. 0.61 +/- 0.33 mmol/l, P = 0.021). In the multivariable analyses of those with diabetes, the two independent risk factors for MA were similar: HbA(1c), OR = 1.13 (1.01, 1.28), and systolic blood pressure, OR = 1.21 (1.04, 1.41). CONCLUSIONS: African-American women with a history of GDM have one of the highest rates for MA. Presence of MA was not associated with insulin resistance but was significantly independently associated with HbA(1c) levels and hypertension. These results, taken in context of the literature, suggest that hypertension and glucose intolerance, in part, influence MA through different mechanisms. Because of the high prevalence of MA in this population and MA's relation to all-cause and cardiovascular mortality, screening for MA should be considered.

Prescription drug use and costs among diabetic patients in primary health care practices in Germany.

OBJECTIVE: To evaluate drug prescriptions and costs among diabetic patients in primary care practices in Germany. RESEARCH DESIGN AND METHODS: Computerized data on prescriptions and costs (drug company sales prices) were analyzed in 30,604 diabetic and 17,723 (5% random sample) nondiabetic patients from 362 primary care practices during 1994. Relative use ratios for drug groups were obtained from logistic regression models (odds ratio [OR] for diabetes) controlling for age, sex, and other covariates. Relative costs (diabetic:nondiabetic) were estimated by direct age and sex standardization. RESULTS: Diabetic patients had an increased prescription use for most drugs. A substantial increased use (OR > or = 1.4) was found for cardiovascular drugs, fibrates, gout medication, laxatives, and wound care products. Diabetic subjects (7.9% of all patients) accounted for 21% of total annual prescription costs in the practices. Total costs (U.S. dollars) per patient-year were threefold higher (diabetic patients $384; control subjects $123). After excluding antidiabetic agents and age- and sex-standardization, relative costs were still 1.5 times higher (P < 0.05). Diabetes treatment accounted for 24% of total costs in diabetic patients (insulin 12%; oral antidiabetics 6%). The most important cost factor was cardiovascular drugs (CVDs) (39%). Three CVD groups accounted for about 50% of total CVD costs in diabetic patients (ACE inhibitors 25%; Ca-antagonists 16%; nitrates 10%). CONCLUSIONS: Prescription use among diabetic patients in primary health care practices was predominantly increased for cardiovascular drugs and for treatment of diabetes-associated disorders. Diabetic patients accounted for over one-fifth of the total pharmacy costs in primary practices, indicating that diabetes is a major economic factor in drug use.

Genes within the major histocompatibility complex predict NIDDM in African-American women in Alabama.

OBJECTIVE: To test the hypothesis that genes within the major histocompatibility complex (MHC) are associated with gestational diabetes mellitus (GDM) and, subsequently, non-insulin-dependent diabetes mellitus (NIDDM) in African-American women. RESEARCH DESIGN AND METHODS: African-American women who presented with GDM were compared with pregnant African-American control subjects. Following pregnancy, GDM patients were assessed at various intervals of time (median = 6 years) to determine whether they had developed diabetes. RESULTS: GDM patients who required insulin during pregnancy possessed a significantly higher frequency of A33, DR2, DR9, and BF-S phenotypes than control subjects. GDM patients who subsequently developed NIDDM had a significantly higher frequency of B41, DR2, and BF-S and a lower frequency of DR1 and DR6 phenotypes than control subjects. Even after controlling for age and body mass index, B41 and DR2 were independent predictors of developing insulin-requiring GDM and NIDDM in GDM subjects. CONCLUSIONS: These results suggest that either one or more genes within the MHC are involved in the etiology of NIDDM.

A positive association between maternal serum zinc concentration and birth weight.

A study was conducted on a cohort of 476 women (364 black, 112 white), who attended the Jefferson County Health Department clinic for their prenatal care, to ascertain the relationship between maternal serum zinc concentration measured early in pregnancy and birth weight. For all subjects maternal serum zinc was significantly related to birth weight after various independent determinants of birth weight were controlled for. The data in this study indicate a threshold for maternal serum zinc concentration below which the prevalence of low birth weight increases significantly. Pregnant women who had serum zinc concentrations in the lowest quartile had significantly higher prevalence of low birth weight than did those mothers who had serum zinc concentrations in the upper three quartiles during pregnancy. These findings suggest that maternal serum zinc concentration measured early in pregnancy could be used to identify those women at higher risk of giving birth to a low-birth-weight infant.

Associations of MHC genes with levels of caries-inducing organisms and caries severity in African-American women.

The aim of this investigation was to evaluate the relationship between MHC alleles at the HLA-DRB1, DQB1 and TNFa microsatellite loci and levels of oral bacteria that play a role in the etiology of dental caries, and the DMFS index in 186 AA primparous women. The average age of the cohort was 20.8+/-3.7 years. The median DMFS index was 9 (range 0-68). High levels of S. mutans were positively associated with DRB1*3 and DRB1*4 presence (p < or = 0.005). DRB1*8 was positively associated with higher levels of S. mutans as a percentage of total Streptococci (p = 0.04). DRB1*1 was positively associated with high levels L. casei (p = 0.04). DQB1 alleles were not observed associated with oral bacterial levels. TNFa allele 103 was negatively associated (p = 0.04), and TNFa 117 was positively associated (p = 0.007), with high levels of L. acidophilus. No significant associations were observed between any DRB1, DQB1 or TNFa allele and the DMFS index. These results support an hypothesis of an association between host HLA class II and TNFa genetic profile and colonization of S. mutans, L. casei, and L. acidophilus thought to be pathogens involved in the etiology of dental caries.

Relations of hyperuricemia with the various components of the insulin resistance syndrome in young black and white adults: the CARDIA study. Coronary Artery Risk Development in Young Adults.

PURPOSE: To assess the association of hyperuricemia with the various components of the Insulin Resistance Syndrome (IRS) in a biracial cohort of young adults. METHODS: Cross-sectional study in 4053 young black and white adults aged 18-30 years from the Coronary Artery Risk Development in Young Adults (CARDIA) study. RESULTS: Body mass index (BMI), fasting insulin, and triglycerides were significantly higher, and high density lipoprotein (HDL)-cholesterol lower in subjects with hyperuricemia (uric acid > or = 7.0 mg/dl in males; > or = 6.0 mg/dl in females) (all p < 0.001). BMI showed the strongest positive correlation with uric acid among the IRS components. Significant associations of hyperuricemia with these risk factors were observed in all sex-race groups, which persisted after controlling for possible confounders including age, education, physical activity, smoking, alcohol intake, oral contraceptive use, and creatinine. Further adjustment for BMI and/or waist-to-hip ratio caused a large decrease in the strength of the associations. Adjustment for insulin also lead to decreases; however, the influence of fasting insulin appeared weaker than obesity. Even after controlling for obesity, insulin, and the other components of the IRS, male subjects in both races in the upper tertile of triglycerides were still more likely to have hyperuricemia. CONCLUSIONS: The association of hyperuricemia with most aspects of the IRS may result predominantly from their covariation with adiposity and secondarily with insulin level. Elevated triglyceride level seems to have an independent relationship with hyperuricemia in males. The relationship between hyperuricemia and cardiovascular disease observed in previous studies may be secondary to its association with the IRS.

Socioeconomic characteristics and melanoma incidence.

PURPOSE: This investigation examines the relationship between socioeconomic status (SES) and melanoma incidence in counties included in the Surveillance, Epidemiology, and End Results Registry (SEER) in the United States from 1973 to 1993. METHODS: Cases included whites, aged at least 15 years, with a morphologic diagnosis of malignant melanoma, residing in one of 199 counties at the time of diagnosis. County level measures of SES including median household income, percentage of high school graduates, and percentage of families below poverty were abstracted from the 1950, 1960, 1970, 1980, and 1990 U.S. Census data. The relationship between SES factors and melanoma rates was examined by hierarchical Poisson regression. RESULTS: The percentage of high school graduates was significantly and positively associated with the incidence of melanoma (relative risk (RR), 1.28; 95% confidence interval (CI), 1.21-1.35), after controlling for age at diagnosis, gender, time period, latitude, and percentage of Hispanics in the county. Percentage of families below poverty was significantly inversely associated with the incidence of melanoma (RR, 0.66; 95% CI, 0.55-0.78). When education and poverty were included in the same model, both the positive effects of education (RR, 1.23; 95% CI, 1.16-1.31) and the negative effects of poverty (RR, 0.85; 95% CI, 0.74-0.98) persisted. In contrast, median household income was not associated with melanoma incidence in a similar multivariable model (RR, 1.00; 95% CI, 0.99-1.00). CONCLUSION: Whether the effect of education on incidence of melanoma reflects lifestyle behaviors that modify exposure to sunlight or some other factor remains unclear. Nonetheless, the findings of this study suggest that the determinant is primarily related to education, not income.

Cardiovascular drug prescriptions and risk of depression in diabetic patients.

Our aim was to investigate the association of calcium channel blocker (CCB), beta-blocker, and ACE inhibitor medications with the risk of depression in diabetic patients. A case-control study was performed using an automated database (MediPlus, IMS) of 400 primary care practices in Germany including 972 diabetic cases with newly diagnosed depression in 1996 (index date) and 972 diabetic controls, matched for age, sex, and index date. The odds ratios (95%-confidence intervals) for depression, adjusted for type of practice, number of visits and prescriptions, hospitalization, cardiovascular diagnoses, and renal failure, were 2.2 (95% CI: 1.2-4.2) for exposure to CCB 6 months prior to index date, 2.6 (95% CI: 1.1-7.0) for beta-blockers, and 1.3 (95% CI: 0.8-2.2) for ACE inhibitors, respectively. Adjusted odds ratio for CCB (4.3; 95% CI: 1.7-13.5) and beta-blockers (4.5; 95% CI: 1.2-29.5) were higher with daily dosages above the median. Prescriptions of CCB and beta-blockers among diabetic patients may increase the risk of depression. Because this association may alternatively be explained by cardiovascular comorbidity, further studies will be necessary to investigate the link between these cardiovascular medications and depression.

Immunity and survival.

Studies in human families and in surviving older persons suggest that the immune system may have an important role in the control of the survival. Immune response (Ir) genes to infectious agents can be detected in human families.

Clinical and biochemical studies on methylxanthine-related fibrocystic breast disease.

The results of this study show that the consumption of methylxanthines through dietary sources appears to be associated with the etiologic development of benign fibrocystic disease in the American woman. Complete abstention from methylxanthine consumption resulted in complete resolution of the disease in 82.5% and significant improvement in 15% of those studied. Thus 97.5% showed clinical benefit from total methylxanthine abstention. The results of a clinical questionnaire answered by 500 women consuming methylxanthines, one half of whom had fibrocystic breast disease, suggest that women with fibrocystic disease may have a genetic predisposition for both benign breast disease and cancer. Biochemical studies implicate increased sensitivity of the adenylate cyclase system to catecholamines in patients with fibrocystic disease. Methylxanthines are known to increase circulating catecholamines.

Biochemical subgrouping of benign breast disease to define premalignant potential.

To determine which subgroups of benign breast disease are likely to progress to malignant degeneration, a biochemical analysis of 3'5' cyclic adenosine monophosphate (cAMP) was run on several samples of breast tissue. cAMP is elevated in a progressive fashion from normal breast tissue to fibrosis, cystic mastitis, ductular hyperplasias, and finally to carcinoma. Correlation of cAMP levels in breast lesions with histopathologic grading of increasing epithelial proliferation confirmed the concept that there are subgroups within those lesions that have greater malignant potential. Benign breast lesions with significantly higher cAMP levels, although still lower than those of cancer, must be considered at higher risk for eventual malignant change.

Pharmacokinetics and urinary excretion of clavulanic acid after oral administration of amoxicillin and potassium clavulanate.

Clavulanic acid is a beta-lactamase inhibitor which prevents microbial lactamase inactivation of beta-lactam antibiotics. The pharmacokinetics and urinary excretion of clavulanic acid were studied in eight healthy adult volunteers after oral administration of 500 mg amoxicillin and 125 mg potassium clavulanate. Serum and urine clavulanic acid concentrations were assayed using high-performance liquid chromatography. Pharmacokinetic parameters were: t 1/2 beta = 1.019 +/- 0.090 hour, t 1/2 alpha = 0.276 +/- 0.031 hour, lag time = 0.321 +/- 0.018 hour, tmax = 1.042 +/- 0.80 hour, Cmax = 2.098 +/- 0.441 micrograms/ml, and AUC = 4.897 +/- 0.979 micrograms X hr/ml. Cumulative urinary excretion of clavulanic acid (as percentage of dose administered) was: 14.05 +/- 2.87 within 2 hours, 25.77 +/- 3.98 within 4 hours, and 27.85 +/- 4.27 within 6 hours after administration.

Associations of properdin factor B with melanoma.

We investigated 98 melanoma patients and 135 normal controls for differences in phenotype and genotype frequencies at the properdin factor B locus. A significant negative association with the Bf-F allele and melanoma was found, resulting in an estimated relative risk of 0.5. The estimated relative risk for developing melanoma among people with the Bf-FF genotype is 0.07. The Bf-S phenotype was significantly increased among the melanoma sample, with an estimated risk of 6.5. The data suggest association of the Bf locus with a melanoma protection and/or susceptibility gene(s).

Allelic variants for complement factors C3, C4, and B in acute necrotizing ulcerative gingivitis.

Impaired immune defense mechanisms and genetic factors appear to play a role in susceptibility to acute necrotizing ulcerative gingivitis (ANUG). Therefore, possible etiological mechanisms might involve genes at the Major Histocompatibility Complex, which include the complement factor loci. We have tested for a possible association between certain complement factor alleles and ANUG using a case-control study design. Specific alleles at complement factors C3 and C4, and properdin factor B (Bf) loci were determined indirectly by high voltage agarose gel electrophoresis in 58 subjects with a history of ANUG and in 58 age-sex-matched healthy controls. The highest relative risk of ANUG, as obtained by conditional logistic regression, for alleles at the C3 locus was 1.9 (90% confidence limits 0.8 to 4.8; p = 0.229) for C3*F-positive individuals. The highest relative risk for alleles at the C4 locus was 2.6 (0.5 to 14.9; p = 0.358) for C4A*3-positive individuals. There was no evidence for an association between Bf allotype and risk of ANUG, with a relative risk of 1.2 for Bf*F- and relative risk of 1.0 for B*S-positive individuals. None of our estimates was statistically significant. We conclude, therefore, that it is unlikely that there is any association between complement factor gene haplotype and susceptibility to ANUG.