# Association of Alanine Aminotransferase and Periodontitis: A Cross-Sectional Analysis—NHANES 2009–2012

Authors: R. Constance Wiener; Usha Sambamoorthi; Richard J. Jurevic
Journal: International Journal of Inflammation
 (2016)

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## Abstract

Objective. Alanine Aminotransferase is an enzyme associated with not only liver diseases, liver conditions, and metabolic syndrome, but also inflammation. Periodontitis is associated with increased cytokines and other markers of inflammation. The purpose of this study is to determine if an independent association between Alanine Aminotransferase and periodontitis exists.Methods. Data from the 2009-2010 and 2011-2012 National Health and Nutrition Surveys (NHANES) were combined. Data concerning periodontitis and Alanine Aminotransferase were extracted and analyzed with Rao Scott Chi-square and logistic regressions. Serum Alanine Aminotransferase was dichotomized at 40 units/liter, and periodontitis was dichotomized to the presence or absence of periodontitis.Results. In bivariate Chi-square analyses, periodontitis and Alanine Aminotransferase were associated (p=0.0360) and remained significant in unadjusted logistic regression (OR = 1.30 [95% CI: 1.02, 1.65]). However, when other known risk factors of periodontitis were included in the analyses, the relationship attenuated and failed to reach significance (adjusted OR = 1.17 [95% CI: 0.85, 1.60]).Conclusion. Our study adds to the literature a positive but attenuated association of serum Alanine Aminotransferase with periodontitis which failed to reach significance when other known, strong risk factors of periodontitis were included in the analysis.


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## Body

## 1. Introduction

Alanine Aminotransferase is an enzyme that is a catalyst in the transfer of –NH2 group from L-alanine to alpha-ketoglutarate creating pyruvate and L-glutamate which are important reactions in the tricarboxylic acid cycle (also known as the Krebs cycle or the citric acid cycle of energy production) [1]. Alanine Aminotransferase is primarily found in hepatocyte intracellular fluid [1]. Serum levels are used to detect hepatic distress and diseases such as chronic viral infections, autoimmune hepatitis, and steatohepatitis, as well as other conditions such as celiac disease, muscle injury, hemochromatosis, and nonalcoholic fatty liver disease [1]. Serum levels also increase with extreme physical exertion, excessive alcohol intake, some medications, and metabolic syndrome [1], the clustering and synergistic effects of interrelated risk factors leading to diseases of chronic inflammation (cardiovascular disease, stroke, and/or diabetes) [2–5]. Many mechanisms and pathways may be involved in elevated serum Alanine Aminotransferase levels; however, chronic inflammation is one potential mechanism for its increase.Periodontitis is the destruction of the soft and hard oral tissue supporting the teeth as the result of a biofilm (bacteria, fungi, and viruses), genetic susceptibility, and plaque-induced chronic inflammation, among other risk factors [6–13]. Systemic chronic inflammation negatively impacts periodontal health. Periodontitis is a public health concern as it is a common disease affecting 46% of US adults (64.7 million individuals) [14]. Periodontitis affects oral health quality of life, the number of remaining teeth in older adults, and glycemic control in individuals with diabetes and has social and financial impacts.The purpose of this study is to determine if there exists an independent association of Alanine Aminotransferase and periodontitis. The theoretical basis is that Alanine Aminotransferase levels are increased with inflammation and periodontitis is a disease of chronic inflammation. Researchers using animal models indicated that such an association exists [15–17]. Researchers also determined that an association of periodontitis and Alanine Aminotransferase existed using a convenience sample of 2225 young Japanese male university students [18]. However, the number of participants with periodontitis was small (4.7%) in that study. The rationale for this study is that there is a need for a large, nationally representative study to determine if an association exits between periodontitis and Alanine Aminotransferase. Such knowledge could help inform decisions by medical personnel concerning dental referrals for patients with high Alanine Aminotransferase levels.The null hypothesis for this research is that the adjusted odds ratio for the association of high levels of serum Alanine Aminotransferase (≥40 units/liter) on periodontitis is the same as the adjusted odds ratio for normal levels of serum Alanine Aminotransferase (<40 units/liter) on periodontitis.


## 2. Materials and Methods

This study was acknowledged by the West Virginia University Institutional Review Board (protocol 14010466515). The study was conducted using the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines.


### 2.1. Data Source

Data used in this study were from the combined 2009-2010 and 2011-2012 National Health and Nutrition Examination Surveys (NHANES) which were collected by researchers from the Centers for Disease Control and Prevention (CDC). The NHANES surveys had a stratified, multistage probability sampling strategy. Noninstitutionalized civilian individuals were selected for the survey. They provided written informed consent. Each participant was interviewed and had a physical evaluation in NHANES MEC (Mobile Examination Center).The periodontal examinations were completed by licensed dentists. He or she had an available halogen light, a HuFriedy™ periodontal probe, and a mouth mirror for each examination. The examination was limited to individuals who were not edentulous and who did not have heart transplants, artificial valves, congenital heart disease, rheumatic fever, hemophilia, kidney disease with dialysis, or a pacemaker.Alanine Aminotransferase level in serum or plasma was determined by NHANES researchers using a kinetic rate method. Alanine Aminotransferase is a catalyst in the reversible reaction of L-alanine and a-ketoglutarate to pyruvate and L-glutamate. In the analysis, the pyruvate is further reduced. The rate of change in absorbance at 340 nm over time is proportional to the Alanine Aminotransferase level [19]. The details of the NHANES procedures are available at http://www.cdc.gov/nchs/nhanes.htm.


### 2.2. Eligible Study Population

The researchers for this study used a subset of the available data from the NHANES 2009–2012 surveys. Eligible participants were aged 30–69 years and had complete data on periodontitis and serum Alanine Aminotransferase. The eligible sample included 5,758 participants.


### 2.3. Dependent Variable

The periodontal variable was the dependent variable for this study. Periodontitis was dichotomized as a yes/no variable to establish an adequate sample size. Even though several years of NHANES data were combined, there were too few participants in the categories of “mild periodontitis” and “severe periodontitis” who also had Alanine Aminotransferase data to use those categories as separate categories. Instead, the categories were no periodontitis (the reference group) and periodontitis (mild, moderate, or severe) using the definition of periodontitis for population-based surveillance supported by the CDC in partnership with the American Academy of Periodontology [20]. Their more detailed definition of periodontitis includes“mild periodontitis” in which there are at least 2 interproximal areas in which the attachment loss is at least 3 mm and there are at least 2 interproximal areas on different teeth in which the probing depth is at least 4 mm or at least one area with a probing depth of 5 mm;“moderate periodontitis” in which there are at least 2 interproximal areas on different teeth in which the attachment loss is at least 4 mm or there are at least 2 interproximal areas on different teeth in which the probing depth is at least 5 mm; and“severe periodontitis” in which there are at least 2 interproximal areas which are on different teeth in which the attachment loss is at least 6 mm and there is at least 1 interproximal area in which the probing depth is at least 5 mm [20].


### 2.4. Independent Variable and Other Variables

The key-independent variable was serum Alanine Aminotransferase. It was dichotomized at <40 units/liter (the reference group) and ≥40 units/liter. The cut-point at ≥40 units/liter is routinely used and has been previously reported in peer-reviewed literature to determine normal and high levels of Alanine Aminotransferase in adults [21–23].The other variables that were included in this study to account for confounding or to further explain the variance for periodontitis included sociodemographic and behavioral variables: sex, race/ethnicity, education, age, income to poverty ratio, smoking, body mass index, insurance coverage, presence of diabetes mellitus, and alcohol consumption. The categories for the additional variables were sex (male versus female), race/ethnicity, (non-Hispanic black, Mexican American, and other versus non-Hispanic white), education (high school, less than high school, and some college versus college degree and above), age (45–54, 55 years and above versus 30–44 years), family income to poverty ratio (less than 2 versus 2 and above), smoking status (current, former smoker versus never smoker), alcohol consumption (moderate, heavy versus no consumption), body mass index (25–29, 30 and above versus 0–24), insurance coverage (no versus yes), and diabetes (yes versus no).


### 2.5. Statistical Analyses

Due to the complex study design, the analysis accounted for clustering, stratification, selected sample population, and sample weights. Descriptions of the sample population, bivariate (Rao Scott Chi-square) analyses with periodontitis, and logistic regression analyses were completed. In logistic regression model development, significant variables from the bivariate analyses (atp<0.05) were included in the model. The statistics package that was used was SAS 9.3® (Cary, NC).


## 2.1. Data Source

Data used in this study were from the combined 2009-2010 and 2011-2012 National Health and Nutrition Examination Surveys (NHANES) which were collected by researchers from the Centers for Disease Control and Prevention (CDC). The NHANES surveys had a stratified, multistage probability sampling strategy. Noninstitutionalized civilian individuals were selected for the survey. They provided written informed consent. Each participant was interviewed and had a physical evaluation in NHANES MEC (Mobile Examination Center).The periodontal examinations were completed by licensed dentists. He or she had an available halogen light, a HuFriedy™ periodontal probe, and a mouth mirror for each examination. The examination was limited to individuals who were not edentulous and who did not have heart transplants, artificial valves, congenital heart disease, rheumatic fever, hemophilia, kidney disease with dialysis, or a pacemaker.Alanine Aminotransferase level in serum or plasma was determined by NHANES researchers using a kinetic rate method. Alanine Aminotransferase is a catalyst in the reversible reaction of L-alanine and a-ketoglutarate to pyruvate and L-glutamate. In the analysis, the pyruvate is further reduced. The rate of change in absorbance at 340 nm over time is proportional to the Alanine Aminotransferase level [19]. The details of the NHANES procedures are available at http://www.cdc.gov/nchs/nhanes.htm.


## 2.2. Eligible Study Population

The researchers for this study used a subset of the available data from the NHANES 2009–2012 surveys. Eligible participants were aged 30–69 years and had complete data on periodontitis and serum Alanine Aminotransferase. The eligible sample included 5,758 participants.


## 2.3. Dependent Variable

The periodontal variable was the dependent variable for this study. Periodontitis was dichotomized as a yes/no variable to establish an adequate sample size. Even though several years of NHANES data were combined, there were too few participants in the categories of “mild periodontitis” and “severe periodontitis” who also had Alanine Aminotransferase data to use those categories as separate categories. Instead, the categories were no periodontitis (the reference group) and periodontitis (mild, moderate, or severe) using the definition of periodontitis for population-based surveillance supported by the CDC in partnership with the American Academy of Periodontology [20]. Their more detailed definition of periodontitis includes“mild periodontitis” in which there are at least 2 interproximal areas in which the attachment loss is at least 3 mm and there are at least 2 interproximal areas on different teeth in which the probing depth is at least 4 mm or at least one area with a probing depth of 5 mm;“moderate periodontitis” in which there are at least 2 interproximal areas on different teeth in which the attachment loss is at least 4 mm or there are at least 2 interproximal areas on different teeth in which the probing depth is at least 5 mm; and“severe periodontitis” in which there are at least 2 interproximal areas which are on different teeth in which the attachment loss is at least 6 mm and there is at least 1 interproximal area in which the probing depth is at least 5 mm [20].


## 2.4. Independent Variable and Other Variables

The key-independent variable was serum Alanine Aminotransferase. It was dichotomized at <40 units/liter (the reference group) and ≥40 units/liter. The cut-point at ≥40 units/liter is routinely used and has been previously reported in peer-reviewed literature to determine normal and high levels of Alanine Aminotransferase in adults [21–23].The other variables that were included in this study to account for confounding or to further explain the variance for periodontitis included sociodemographic and behavioral variables: sex, race/ethnicity, education, age, income to poverty ratio, smoking, body mass index, insurance coverage, presence of diabetes mellitus, and alcohol consumption. The categories for the additional variables were sex (male versus female), race/ethnicity, (non-Hispanic black, Mexican American, and other versus non-Hispanic white), education (high school, less than high school, and some college versus college degree and above), age (45–54, 55 years and above versus 30–44 years), family income to poverty ratio (less than 2 versus 2 and above), smoking status (current, former smoker versus never smoker), alcohol consumption (moderate, heavy versus no consumption), body mass index (25–29, 30 and above versus 0–24), insurance coverage (no versus yes), and diabetes (yes versus no).


## 2.5. Statistical Analyses

Due to the complex study design, the analysis accounted for clustering, stratification, selected sample population, and sample weights. Descriptions of the sample population, bivariate (Rao Scott Chi-square) analyses with periodontitis, and logistic regression analyses were completed. In logistic regression model development, significant variables from the bivariate analyses (atp<0.05) were included in the model. The statistics package that was used was SAS 9.3® (Cary, NC).


## 3. Results

Table1 has the results of the sample description. There were 5758 eligible participants, 50.1% of whom were female. Considering race/ethnicity, 68.1% of participants were non-Hispanic white, 10.6% of participants were non-Hispanic black, and 8.4% of participants were Mexican American. There were 41.9% of participants who were aged 30–44 years; 28.7% of participants who were 45–54 years; and 29.4% of participants who were 55–69 years. There were 64.2% of participants who attended some college courses, technical school courses, or above. Most had an income to poverty ratio above 2.0 (69.9%). There were 56.1% of participants who were never smokers and 20.5% of participants who never used alcohol. There were 27.0% of participants who had a body mass index of 0–24, 36.0% of participants who had a body mass index of 25–29, and 37.0% of participants who had a body mass index of 30 and above. There were 12.1% of participants who had ≥40 units/liter Alanine Aminotransferase and 39.9% of participants who had periodontitis.Table 1
Sample characteristics, NHANES 2009–2012,n=5758.
Number
Weighted percentage
Alanine Aminotransferase (serum)
<40 units/liter (normal)
5,062
87.9
≥40 units/liter
696
12.1
Periodontitis
No
2,946
60.1
Yes
2,812
39.9
Mild
207
3.0
Moderate
2,048
30.1
Severe
557
6.9
Sex
Male
2,884
49.9
Female
2,874
50.1
Race/ethnicity
Non-Hispanic white
2,308
68.1
Non-Hispanic black
1,231
10.6
Mexican American
932
8.4
Other
1,287
13.0
Age
30–44 years
2,407
41.9
45–54 years
1,536
28.7
55–69 years
1,815
29.4
Education
Less than HS
1,393
15.5
HS graduate
1,218
20.4
Some coll./tech.
1,613
29.6
Coll./tech. graduate
1,527
34.6
Family income to poverty ratio
0 to less than 2.00
2,417
30.1
2.00 and above
2,853
69.9
Alcohol consumption
Nonuse
1,293
20.5
Moderate use
2,041
51.1
Heavy use
1,391
28.4
Smoking status
Current
1,219
19.0
Former
1,307
24.9
Never
3,229
56.1
Body mass index
0–24
1,478
27.0
25–29
1,995
36.0
30 and above
2,252
37.0
Insurance
Yes
4,178
79.3
No
1,580
20.7
Diabetes
Yes
732
18.0
No
2,394
82.0
SE: standard error of row percent; HS: high school; and  coll./tech.: college technical school.The Chi-square bivariate analyses and standard errors are presented in Table2. There was a significant relationship (p=0.0360) of serum Alanine Aminotransferase levels ≥40 U/L and periodontitis. Other significant relationships (at p<0.0001) were with periodontitis and sex; race/ethnicity; age; education; family income to poverty ratio; alcohol consumption; smoking status; insurance coverage; and diabetes mellitus. Body mass index was also significant at p=0.0151.Table 2
Periodontitis status in Rao Scott Chi-square analysis,   NHANES, 2009–2012.
Frequency negative
Weighted row%
Frequency Positive
Weighted row%
SE
p value
Alanine Aminotransferase (serum)
0.0360
<40 units/liter (normal)
2623
60.8
2439
39.2
1.5
≥40 units/liter
323
54.5
373
38.2
3.1
Sex
<0.0001
Male
1185
50.9
1699
49.1
1.5
Female
1761
69.2
1113
30.8
1.7
Race/ethnicity
<0.0001
Non-Hispanic white
1445
65.9
863
34.1
1.9
Non-Hispanic black
502
45.5
729
54.5
2.5
Mexican American
350
41.4
582
58.6
1.8
Other
649
53.1
638
46.9
2.1
Age
<0.0001
30–44 years
1602
70.0
805
27.0
1.5
45–54 years
715
55.7
821
44.3
2.2
55–69 years
629
45.8
1186
54.2
2.1
Education
<0.0001
Less than HS
446
35.7
947
64.6
1.6
HS graduate
529
51.1
689
48.9
2.4
Some coll./tech.
884
59.6
729
40.4
1.9
Coll./tech. graduate
1084
76.9
443
23.1
1.5
Family income to poverty ratio
<0.0001
0 to less than 2.00
986
45.8
1431
54.1
1.6
2.00 and above
1753
67.1
1100
32.9
1.6
Alcohol consumption
<0.0001
Nonuse
643
57.9
659
42.1
2.4
Moderate use
1257
68.8
784
31.2
1.8
Heavy use
587
50.2
804
40.8
2.3
Smoking status
<0.0001
Current
400
35.3
819
64.7
1.9
Former
620
58.3
687
41.7
2.5
Never
1926
69.3
1303
30.7
1.3
Body mass index
0.0151
0–24
805
63.2
673
36.8
1.8
25–29
1014
60.2
981
39.8
1.6
30 and above
1109
57.7
1143
42.3
2.0
Insurance
<0.0001
Yes
2346
64.6
1832
35.4
1.5
No
600
42.7
980
57.3
2.0
Diabetes
<0.0001
Yes
244
48.0
488
59.2
3.2
No
1299
50.7
1095
38.2
1.9
SE: standard error of row percent; HS: high school; and  coll./tech.: college or technical school.Table3 has the results of the logistic regression of serum Alanine Aminotransferase on periodontitis. The odds ratio, in unadjusted logistic regression, for periodontitis associated with higher levels of serum Alanine Aminotransferase was 1.30 (95% confidence interval: 1.02, 1.65).Table 3
Logistic regression of serum  Alanine Aminotransferase on periodontal status:   NHANES, 2009–2012.
Unadjusted OR (95% CI)
Adjusted OR (95% CI)
Periodontitis
Yes
1.30 (1.02, 1.65)
1.17 (0.85, 1.60)
No
1.00 (reference)
1.00 (reference)
Sex
Male
2.55 (2.07, 3.15)
Female
1.00 (reference)
Race/ethnicity
Non-Hispanic white
1.00 (reference)
Non-Hispanic black
2.07 (1.50, 2.86)
Mexican American
2.21 (1.52, 3.23)
Other
1.63 (1.13, 2.37)
Education
Less than high school
2.62 (1.67, 4.12)
High school
1.71 (1.20, 2.44)
Some college
1.31 (0.94, 1.82)
College degree or above
1.00 (reference)
Family income to poverty ratio
Less than 2.00
1.36 (1.06, 1.73)
2.00 and above
1.00 (reference)
Insurance coverage
No
1.74 (1.14, 2.68)
Yes
1.00 (reference)
Body mass index
0 to less than 25
1.00 (reference)
25 to less than 30
0.98 (0.66, 1.46)
30 and above
0.92 (0.63, 1.32)
Smoking
Yes
3.26 (2.28, 4.68)
No
1.00 (reference)
Alcohol consumption
Heavy
0.92 (0.63, 1.34)
Moderate
0.66 (0.47, 0.93)
None
1.00 (reference)
Diabetes
Yes
1.32 (0.93, 1.87)
No
1.00 (reference)
OR: odds ratio; AOR: adjusted odds ratio; CI: confidence interval.An Adjusted Model was created which included sex (male versus female), race/ethnicity, (non-Hispanic black, Mexican American, and other versus non-Hispanic white), education (high school, less than high school, and some college versus college degree and above), age (45–54, 55 years and above versus 30–44 years), family income to poverty ratio (less than 2 versus 2 and above), smoking status (current, former smoker versus never smoker), alcohol consumption (moderate, heavy versus no consumption), body mass index (25–29, 30 and above versus 0–24), insurance coverage (no versus yes), and diabetes (yes versus no). The adjusted odds ratio for periodontitis associated with higher levels of serum Alanine Aminotransferase was 1.17 (95% confidence interval: 0.85, 1.60).


## 4. Discussion

In this study we evaluated the relationship of Alanine Aminotransferase on periodontitis in a large, nationally representative sample of 5758 participants. The results of this study included an initial significant association of Alanine Aminotransferase with periodontitis (odds ratio 1.30, 95% CI, 1.02, 1.65), which remained positive but attenuated and failed to reach significance with the addition of other variables (adjusted odds ratio 1.17, 95% CI, 0.85, 1.60). Serum Alanine Aminotransferase was dichotomized at <40 units/liter (the reference group) and ≥40 units/liter in this study, although other researchers have used lower cut-points, such as ≥30 units/liter [24], and some researchers have used a higher level such as ≥41 units/liter [18]. When a cut-point of ≥30 units/liter was used with these data, the adjusted odds ratio was 1.16 (95% CI, 0.90, 1.50) and when a cut-point of ≥41 units/liter was used with these data, the adjusted odds ratio was 1.26 (0.89, 1.77).The results of this study are similar to the results of researchers studyingsalivary Alanine Aminotransferase in a sample of 50 participants in Romania. They determined that salivary Alanine Aminotransferase was not statistically different among individuals who had periodontitis as compared with individuals who did not have periodontitis [25]. The study in Romania differed from this current study in the source of Alanine Aminotransferase (saliva rather than blood or serum) and study population size.It has been suggested that changes in enzymatic activity indicate metabolic change in inflammation and that Alanine Aminotransferase release increases with cell injury and death. Researchers in a study of 49 older adult Japanese patients with chronic periodontitis found Alanine Aminotransferase to be associated with periodontal inflammation [26]. Several of the same researchers conducted an 18-month longitudinal study of 85 patients with chronic periodontitis in four Japanese university hospitals and found thatsalivary Alanine Aminotransferase in combination with the ratio ofPorphyromonas gingivalis to total bacteria had a sensitivity of 0.4 and a specificity of 0.96 for the prediction of the progression of periodontitis [27].Salivary Alanine Aminotransferase was increased in individuals with periodontitis disease, as compared with controls in a study of 40 patients in India [28]. Researchers found a correlation of salivary Alanine Aminotransferase and periodontitis in a sample of 60 participants [28]. These existing studies differed from the current study in that they were small and the researchers usedsalivary Alanine Aminotransferase for analyses.In a study conducted in Japan withserum Alanine Aminotransferase, a positive association of elevated serum Alanine Aminotransferase and pocket depth was present only in males with low alcohol consumption and at least 3 components of the metabolic syndrome (waists at or above 90 cm in males and 80 cm in females; triglycerides at or above 150 mg/dL or treatment for triglycerides; high density lipoprotein below 40 mg/dL in males or below 50 mg/dL for females; systolic blood press at or above 130 mmHg or diastolic blood pressure at or above 85 or medication for high blood pressure; and fasting glucose at or above 100 mg/dL or treatment for elevated glucose) [29].Researchers who conducted a systematic review with the association of Alanine Aminotransferase on mortality indicated that Alanine Aminotransferase had a complex and inconsistent relationship, which was more predictive in older adults with extremely low levels of Alanine Aminotransferase [30]. The method of collection of the Alanine Aminotransferase was not discussed in the review of the 12 articles selected for the meta-analysis [30].


### 4.1. Strengths, Limitations, and Sources of Bias

Research concerning Alanine Aminotransferase and periodontitis is lacking. Alanine Aminotransferase collection methods differ among researchers and researchers have used different cut-points for Alanine Aminotransferase as well as different definitions for periodontitis.Our study strengths are its large, nationally representative sample; the use of definitions for population-based surveillance of the CDC in partnership with the American Academy of Periodontology; standardized blood testing procedures for Alanine Aminotransferase; and standardized/calibrated examiners. Since this study is large, many variables were included in the multivariable analysis which are also independently related to periodontitis or may confound the relationship of Alanine Aminotransferase and periodontitis, an option that is not available for small studies.Our study limitations are the biases associated with self-reporting of education, income, insurance status, alcohol consumption, and the reporting of diabetes mellitus. It is possible that self-reports may be influenced by participants’ desires for providing a socially desirable response. However, it would be expected that social desirability bias would likely result in reports which would tend to direct the outcome to supporting the null hypothesis that the odds ratio for the association of high Alanine Aminotransferase and periodontitis is the same as the odds ratio for normal levels of Alanine Aminotransferase and periodontitis. Another limitation was not having enough participants to further refine periodontitis as “mild,” “moderate,” and “severe.”


## 4.1. Strengths, Limitations, and Sources of Bias

Research concerning Alanine Aminotransferase and periodontitis is lacking. Alanine Aminotransferase collection methods differ among researchers and researchers have used different cut-points for Alanine Aminotransferase as well as different definitions for periodontitis.Our study strengths are its large, nationally representative sample; the use of definitions for population-based surveillance of the CDC in partnership with the American Academy of Periodontology; standardized blood testing procedures for Alanine Aminotransferase; and standardized/calibrated examiners. Since this study is large, many variables were included in the multivariable analysis which are also independently related to periodontitis or may confound the relationship of Alanine Aminotransferase and periodontitis, an option that is not available for small studies.Our study limitations are the biases associated with self-reporting of education, income, insurance status, alcohol consumption, and the reporting of diabetes mellitus. It is possible that self-reports may be influenced by participants’ desires for providing a socially desirable response. However, it would be expected that social desirability bias would likely result in reports which would tend to direct the outcome to supporting the null hypothesis that the odds ratio for the association of high Alanine Aminotransferase and periodontitis is the same as the odds ratio for normal levels of Alanine Aminotransferase and periodontitis. Another limitation was not having enough participants to further refine periodontitis as “mild,” “moderate,” and “severe.”


## 5. Conclusion

Our study adds to the literature a positive but attenuated association of periodontitis and Alanine Aminotransferase which failed to reach significance when other known, strong factors of periodontitis were included in the analysis.



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