Celiac Disease: Association with Iron Deficiency in Caucasians but Not in Non-Caucasians.
Authors: Murray Joseph A. , McLachlan Stela , Adams Paul C. , Eckfeldt John H. , Garner Chad P. , Vulpe Chris D. , Gordeuk Victor R. , Brantner Tricia L. , Leiendecker-Foster Catherine , Killeen Anthony A. , Acton Ronald T. , Barcellos Lisa F. , Beckman Kenneth B. , McLaren Gordon D. , McLaren Christine E. 
Published: October 2019

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.