Brantner, Tricia L.

Abstract It is well-recognized that Helicobacter pylori infection causes gastrointestinal blood loss and iron deficiency. H. pylori gastritis has also been implicated in iron deficiency refractory to oral iron replacement therapy. Although H. pylori infection is common in multiple populations, less is known about the extent to which H. pylori contributes to iron deficiency in different racial/ethnic groups. To address this question, we tested the serum collected from men aged ≥ 25 y and women ≥ 50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study to identify those with iron deficiency (defined as serum ferritin ≤ 12 mg/L [cases]) and iron-replete controls (serum ferritin > 100 mg/L in men, serum ferritin > 50 mg/L in women). All samples were tested for H. pylori IgG antibodies and for antibodies to CagA (cytotoxin-associated gene-bearing strain). We tested 571 cases and 1142 controls. Participants were considered to have evidence of H. pylori infection if they had positive results for both antibodies or for either antibody alone. Participants who did not have a result for either test were excluded. We examined the association between the presence of H. pylori in cases and controls among Caucasians, Asian/Pacific Islanders, African Americans, and Hispanics. Among Caucasians, evidence of H. pylori infection was comparable in cases and controls; 170 of 735 controls (23.1%) and 97 of 363 cases (26.7%), respectively, were positive. Similar results were found in African Americans (56.3% of 144 controls; 55.8% of 77 cases) and Hispanics (66.7% of 159 controls; 59.5% of 79 cases). However, in Asian/Pacific Islanders, the prevalence of H. pylori was higher among cases (62.8% of 51) than controls (44.1% of 102), p=0.029 by the likelihood ratio Chi-Square test. The relative risk (RR) of iron deficiency among those with H. pylori-positivity was significantly greater than in those without (RR, 1.66; 95% CI [1.04, 2.66]). A comparison of subgroups by positivity for IgG or CagA showed that the relative risk of iron deficiency was increased among those with IgG positivity, with or without Cag A positivity (RR, 1.80 and 1.90, respectively), but not among those with CagA positivity alone (RR, 1.00). H. pylori infection is a frequent contributor to iron deficiency but is also common in the general population. Our results indicate that among HEIRS Study Asian/Pacific Islander participants, H. pylori infection is more prevalent in cases with iron deficiency than in controls. In contrast, there was no difference in the prevalence of H. pylori infection between cases and controls among Caucasians, African Americans, and Hispanics. These results have implications for the investigation of iron deficiency in Asians and Pacific Islanders. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 2095 Celiac disease (CD) is an increasingly recognized disorder in Caucasian populations of European origin. Little is known about its prevalence in non-Caucasians. While CD is thought to be a cause of iron deficiency anemia, the extent to which CD contributes to iron deficiency in Caucasians and especially non-Caucasians is unknown. Iron deficiency is one of the most common nutritional deficiencies in both the developed world and in developing countries. Thus, it is important to know the prevalence of CD in different populations and in iron-deficient and iron-replete persons. To answer these questions, we tested serum collected from Caucasian and non-Caucasian men aged ≥ 25 y and women ≥ 50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. In the HEIRS Study, 101,168 participants were screened with serum biochemical tests of iron status, which not only detected participants with iron overload but also identified a unique multiethnic population of participants with iron deficiency. We hypothesized that CD is more common in those with iron deficiency than in iron-replete individuals. We also examined the difference in frequency of CD between Caucasians and non-Caucasians with iron deficiency. Cases with iron deficiency (defined as serum ferritin ≤ 12 μg/L [cases]) and iron-replete controls (serum ferritin > 100 μg/L in men, serum ferritin > 50 μg/L in women) were further evaluated by using a sequential serological testing scheme whereby all samples were tested with an ELISA for human recombinant tissue transglutaminase IgA antibodies, and positive values were confirmed by endomysial antibodies. Those positive for both tests were considered double positives and were presumed to have untreated CD. Those positive for tissue transglutaminase IgA antibodies but not for endomysial antibodies were termed single positives and were considered indeterminate and excluded from analysis. We further hypothesized that low serum ferritin and an appropriate human leukocyte antigen (HLA) variant, may be predictive of CD. We used SNP-based analysis to determine HLA genotype and DQ8, DQ2.2 or DQ4, and DQ2.5 risk variants. Fisher's exact test was used to examine the association between iron−deficient case and control status and the presence of celiac disease. Log-binomial regression was applied to estimate the odds of celiac disease in iron-deficient cases relative to that of controls. A total of 1713 subjects were tested for tissue transglutaminase IgA antibodies. Participants included 1100 Caucasians, 221 African Americans, 153 Asians, and 239 Hispanics. Fourteen of 571 iron-deficient cases were positive for the double serology compared to just one of 1142 controls. All of the seropositive tests were seen in Caucasians and none in the non-Caucasians. Excluding data from participants with indeterminate serological screen results (6 Caucasians, 4 non-Caucasians), we found that CD occurred in 14 of 567 cases (2.5%) and in only 1 of 1136 (0.1%) controls (Fisher's exact test, p=1.92 10−6). CD was more common in Caucasian cases (14 of 363, 4%) than in non-Caucasian cases (0 of 204, p=0.003). Only one Caucasian control and none of the non-Caucasian controls had CD. The odds of CD in individuals with iron deficiency was 28 (3.7, 212.8) times that in controls. Thirteen of 14 iron-deficient cases with CD carried the DQ2.5 variant of the HLA genotype. Presence of DQ2.5 was highly significantly associated with celiac disease status in iron-deficient cases compared to controls (Fisher's exact test, p = 7.183 × 10−8). The results indicate that CD is a small but significant contributor to iron deficiency in Caucasians. CD is very rare in other races, even among individuals with features frequently seen in CD, such as iron deficiency. CD is also rare in Caucasians who are iron replete. CD testing should be considered for adult Caucasian males or post-menopausal females having iron deficiency without evidence of other etiologies such as gastrointestinal blood loss. Patients identified with CD may benefit from appropriate treatment. Disclosures: No relevant conflicts of interest to declare.

SummaryBackgroundCoeliac disease is a substantially underdiagnosed disorder, with clinical testing currently guided by case finding.AimTo determine the presence of indications for diagnostic testing and frequency of clinical testing in undiagnosed coeliac disease.MethodsThis was a case‐control study of adults without prior diagnosis of coeliac disease. Undiagnosed cases were identified through sequential serology, and unaffected age‐ and gender‐matched controls were selected. Medical records were systematically reviewed for indications for and evidence of clinical testing.ResultsOf 47 557 adults, 408 cases of undiagnosed coeliac disease were identified. 408 serology negative matched controls were selected. Eight‐matched pairs were excluded, leading to 800 included individuals (61% female; median age 44.2 years). The odds of any indication for clinical testing were similar among undiagnosed coeliac disease and controls (odds ratio (OR) 1.18; 95% CI: 0.85‐1.63, P = 0.32). Most individual indications were not associated with serologic status. Exceptions to this include hypothyroidism, which was more likely in cases of undiagnosed coeliac disease, and dyspepsia and chronic diarrhoea, which were less likely. Cases of undiagnosed coeliac disease were more likely to develop osteoporosis (P = 0.005), dermatitis herpetiformis (P = 0.006), chronic fatigue (P = 0.033), thyroiditis (P = 0.003), autoimmune diseases (P = 0.008), and have a family member diagnosed with coeliac disease (P = 0.001).ConclusionThis study strongly suggests that current case finding is not effective in detecting undiagnosed coeliac disease. Individuals with undiagnosed coeliac disease were more likely than controls to develop indications for testing overtime. A more effective method for detection of coeliac disease is needed.