Mercury Exposure and Antinuclear Antibodies Among Females of Reproductive Age in the United States: NHANES

Emily C. Somers; Martha A. Ganser; Jeffrey S. Warren; Niladri Basu; Lu Wang; Suzanna M. Zick; Sung Kyun Park

Disclosures

Environ Health Perspect. 2015;123(8):792-798. 

In This Article

Results

Participant Characteristics

Characteristics of the study population, according to ANA positivity, are summarized in Table 1. Sociodemographics were largely similar for ANA-positive and -negative persons, although in the first cycle there was a larger proportion of non-Hispanic whites and Mexican Americans among ANA positives (p = 0.08). In the combined three-cycle population, education level differed between ANA-positive and -negative groups, with a higher proportion of ANA-positive adults having less than a high school education (p = 0.04). Among ANA-positive compared with negative participants, hair and total blood mercury levels in cycle 1 were higher (p = 0.03 and p = 0.06, respectively), and blood mercury in the three-cycle population was nonsignificantly higher.

ANAs and Mercury

The weighted proportion of participants with ANA positivity was 12% for cycle 1 and 16% for cycles 1–3. Among ANA positives, the speckled pattern was predominant (> 94%; Table 1). The geometric means (geometric SDs) for mercury corresponding to all participants included in Table 1 for whom data were available were as follows: hair, 0.22 (0.03) ppm; total blood, 0.92 (0.05) μg/L; urine, 0.62 (0.04) μg/L. Correlations between the sources of mercury in cycle 1 were as follows: hair and total blood (r = 0.69; p < 0.01), hair and urine (r = 0.34; p < 0.01), total blood and urine (r = 0.41; p < 0.01). Among the females in this study, 12.8% had a total blood mercury level > 3.5 μg/L, the reference dose extrapolated from the U.S. Environmental Protection Agency cord blood mercury reference dose of 5.8 μg/L (Mahaffey et al. 2004; Stern and Smith 2003).

Based on multivariable logistic regression (Table 2), we detected positive and statistically significant associations [confidence intervals (CIs) > 1] between ANA positivity and hair and total blood mercury, but not urinary mercury. From the multivariable models incorporating omega-3 fatty acids (Model B), the adjusted OR for ANA positivity comparing females in the highest versus lowest tertile of hair mercury was 4.10 (95% CI: 1.66, 10.13), and for the highest versus lowest quartile of blood mercury was 2.32 (95% CI: 1.07, 5.03).

We performed sensitivity analyses including BMI and CRP as covariates in the logistic regression models for all mercury types and found no substantive changes in results. Likewise, in separate sensitivity analyses incorporating each PCB summary measure, the mercury associations with ANA positivity remained similar (see Supplemental Material, Table S1 http://ehp.niehs.nih.gov/wp-content/uploads/123/8/ehp.1408751.s001.508.pdf). Of the eight study participants (0.78 weighted percent) reporting utilization of a prescription drug associated with drug-induced autoimmunity (four using carbamazepine, four using minocycline), none were ANA positive. In the urinary mercury sensitivity analyses excluding participants with GFR < 60 mL/min/1.73 m2, there were no substantive changes in results.

Spline regression models showed a nonlinear dose–response relationship for log-transformed hair and total mercury (Figure 1). To examine mercury as a continuous variable, we fit adjusted piecewise logistic regression models, with cut points based on visual inspection of the spline graphs. The dose–response relationship for both hair and total blood mercury increased in a statistically significant fashion within the lower ranges of mercury exposure (through –1 ppm log hair mercury and 0 μg/L log total blood mercury) and then plateaued.

Figure 1.

Associations of antinuclear antibody (ANA) positivity with log-transformed hair and total blood mercury (Hg), adjusted for Model B covariates. (A) Hair Hg (1999–2000; n= 452). (B) Total blood Hg (1999–2004; n= 1,352). Solid black lines represent the smoothing trends estimated from the natural spline with 3 degrees of freedom (df) for hair Hg and 4 df for total blood Hg (knots at 25th, 50th, and 75th percentiles); red dotted lines represent 95% CIs; and bars represent the weighted density distribution for Hg. The dose–response relationship for both hair and total blood Hg increased in a statistically significant fashion within the lower ranges of Hg exposure.

We also evaluated strength of ANA titer as an outcome. For both hair and total blood mercury, compared with the lowest mercury quantile, the upper quantiles contained a substantially higher proportion of individuals with high-titer ANA (≥ 1:1,280; Figure 2). Consistent with the logistic regression models, results from multinomial logistic regression (see Supplemental Material, Table S2 http://ehp.niehs.nih.gov/wp-content/uploads/123/8/ehp.1408751.s001.508.pdf) demonstrated a significant association between hair and total blood mercury, but not urinary mercury, and ANA positivity (data for urinary mercury not shown). Further, magnitudes of association were strongest for high-titer ANA (≥ 1:1,280), where adjusted ORs were > 10 for hair mercury and > 4 for total blood mercury.

Figure 2.

Weighted proportions of antinuclear antibody (ANA) positivity and titer categories according to mercury (Hg) exposure quantiles. (A) Hair Hg (1999–2000; n= 452). (B) Total blood Hg (1999–2004; n= 1,352). (C) Urinary Hg (1999–2002; n= 804).

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