gustinprop: Gustin Gene Polymorphism and 6-n-propylthiouracil (PROP) Taste

• Sponsor: University of Cagliari (Other)
• Overall Status: Completed
• CT.gov ID: NCT01097915
• Collaborator: (none)
• Enrollment: 170
• Location: 1
• Duration (Months): 80
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The investigators evaluate the possible association of PROP taste with gustin gene polymorphism rs2274333 (A/G), salivary zinc ion concentration and BMI. In addition, it has also been evaluated PROP taste sensitivity by recording monophasic potentials from the tongue.

Condition or Disease	Intervention/Treatment	Phase
Dysgeusia

Detailed Description

The investigators evaluate the possible association of PROP taste with gustin gene polymorphism rs2274333 (A/G), salivary zinc ion concentration and BMI.

Furthermore, we apply direct measures of the gustatory system activation following stimulation with PROP, obtained by electrophysiological recordings from the tongue of subjects classified for taster status, genotyped for the specific receptor gene (TAS2R38), and in which papilla density was determined.

Study Design

• Study Type: Observational
• Actual Enrollment: 170 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Sensitivity to 6-n-propylthiouracil (PROP) Association With Gustin (CA6) Gene Polymorphism, Salivary Zinc and BMI in Humans
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
PROP taste sensitivity PROP Sensitive and non sensitive individuals are defined as "Tasters" and "Non-tasters", respectively. Taster are further divided in "Super-taster" who perceived PROP as extremely bitter and "Medium tasters" who perceived PROP as moderately bitter.

Outcome Measures

Primary Outcome Measures

1. Association Between Gustin Gene Polymorphism and PROP Sensitivity [7 months]

   We examine associations between PROP status and the polymorphism rs2274333 (A/G) of the gene that codify for the salivary protein, gustin/CA6, Which has been suggested as a trophic factor that promotes growth and development of taste buds by acting on taste bud stem cells. The intensity of taste perception evoked by PROP and NaCl solutions was estimated to evaluate PROP taster status and molecular analysis of the gustin gene polymorphism was performed in individuals classified by PROP status using PCR techniques.

Secondary Outcome Measures

1. Association Between PROP Sensitivity and Saliva Zinc Ion Concentration [7 months]

   Since the enzymatic function of gustin (CA6) depends upon the presence of Zn at its active site we measured the salivary zinc ion concentration in subjects classified as super-taster, medium taster and non-taster.The salivary Zn2+ concentration was measured with a QuantiChromTM zinc Assay kit (Gentaur, Brussels, Belgium) where the color intensity is directly proportional to the Zn2+ concentration in the sample.

2. Association Between PROP Sensitivity and BMI [7 months]

   Since individual ability to taste PROP may be correlated with BMI, we determined BMI (kg/m^2) in subjects classified as super-taster, medium taster and non-taster.Weight (kg) and height (m) were recorded for each subject.

3. Electrophysiological Recordings From the Tongue for the Objective Evaluation of Individual Variations of 6-n-propylthiouracil (PROP) Sensitivity [1 year]

   electrophysiological recordings from the tongue of 43 subjects classified for their taste sensitivity to 6-n- propyltiouracil (PROP) and genotyped for the specific receptor gene, TAS2R38. Density of fungiform papillae was also determined in each subject. The biopotentials were recorded by means of differential electrophysiological derivations between two silver electrodes, one in contact with the ventral surface of the tongue and one in perfect adhesion with the dorsal surface.

4. Association Between PROP Sensitivity and Fungiform Papilla Density [6 months]

   43 subjects were classified for their taste sensitivity to 6-n- propyltiouracil (PROP) and density of fungiform papillae was determined in each subject.

5. Taste Perception of Sweet, Sour, Salty, Bitter and Umami and Changes Due to L-Arginine Supplementation, as a Functin of Genetic Ability to Taste PROP. [8 months]

   Taste perception was assessed by testing the ability to recognize, and the responsiveness to, representative solutions of the five taste qualities, also when supplemented with L-Arg, in subjects classified as PROP-tasters.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• no variation of body weight > 5 kg over the last 3 mo BMI within 20-25 Age between 20-30

Exclusion Criteria:

• gustatory impairment following a prescribed diet or using medications that might interfere with taste perception food allergies smokers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sezione di Farmacologia Clinica del Dipartimento di Neuroscienze, San Giovanni di Dio Azienda Ospedaliero Universitaria di Cagliari	Cagliari	Ca	Italy	09124

Sponsors and Collaborators

• University of Cagliari

Investigators

• Principal Investigator: Iole Tomassini Barbarossa, PhD, Dip. Scienze Biomediche Sezione di Fisiologia Università di Cagliari

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Iole Tomassini Barbarossa, Associate Professor, University of Cagliari
• ClinicalTrials.gov Identifier: NCT01097915
• Other Study ID Numbers: UNICADBSITB-1
• First Posted: Apr 2, 2010
• Last Update Posted: Dec 21, 2018
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Iole Tomassini Barbarossa, Associate Professor, University of Cagliari: PROP taste sensitivity; Gustin (CAVI) polymorphism; Salivary zinc; BMI; Electrophysiological recording from the tongue
• Additional relevant MeSH terms: Dysgeusia

Study Results

Participant Flow

Arm/Group Title	Super Tasters	Medium Tasters	Non Tasters
Arm/Group Description	Subjects highly sensitive to PROP	Subjects sensitive to PROP	Subjects no sensitive to PROP
Period Title: Overall Study
STARTED	50	70	50
COMPLETED	27	28	20
NOT COMPLETED	23	42	30

Baseline Characteristics

Arm/Group Title	Super Tasters	Medium Tasters	Non Tasters	Total
Arm/Group Description	Subjects highly sensitive to PROP	Subjects sensitive to PROP	Subjects no sensitive to PROP	Total of all reporting groups
Overall Participants	50	70	50	170
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	50 100%	70 100%	50 100%	170 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25 (7)	25 (8)	25 (6)	25 (7)
Sex: Female, Male (Count of Participants)
Female	35 70%	40 57.1%	34 68%	109 64.1%
Male	15 30%	30 42.9%	16 32%	61 35.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	50 100%	70 100%	50 100%	170 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Italy	50 100%	70 100%	50 100%	170 100%
healthy volunteers (participants) [Number]
Number [participants]	50 100%	70 100%	50 100%	170 100%

Outcome Measures

1. Primary Outcome

Title	Association Between Gustin Gene Polymorphism and PROP Sensitivity
Description	We examine associations between PROP status and the polymorphism rs2274333 (A/G) of the gene that codify for the salivary protein, gustin/CA6, Which has been suggested as a trophic factor that promotes growth and development of taste buds by acting on taste bud stem cells. The intensity of taste perception evoked by PROP and NaCl solutions was estimated to evaluate PROP taster status and molecular analysis of the gustin gene polymorphism was performed in individuals classified by PROP status using PCR techniques.
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Super Tasters	Medium Tasters	Non Tasters
Arm/Group Description	Subjects highly sensitive to PROP	Subjects sensitive to PROP	Subjects no sensitive to PROP
Measure Participants	27	28	20
Genotype AA	85.19 170.4%	50.99 72.8%	25.00 50%
Genotype AG	14.81 29.6%	35.71 51%	20 40%
Genotype GG	0 0%	14.29 20.4%	55 110%
Allele A	92.59 185.2%	67.86 96.9%	35 70%
Allele G	7.40 14.8%	32.14 45.9%	65 130%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Super Tasters, Medium Tasters, Non Tasters
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Association Between PROP Sensitivity and Saliva Zinc Ion Concentration
Description	Since the enzymatic function of gustin (CA6) depends upon the presence of Zn at its active site we measured the salivary zinc ion concentration in subjects classified as super-taster, medium taster and non-taster.The salivary Zn2+ concentration was measured with a QuantiChromTM zinc Assay kit (Gentaur, Brussels, Belgium) where the color intensity is directly proportional to the Zn2+ concentration in the sample.
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Super-tasters	Medium Tasters	Non-tasters
Arm/Group Description	Subjects highly sensitive to PROP	Subjects sensitive to PROP	Subjects no sensitive to PROP
Measure Participants	27	28	20
Mean (Standard Error) [microg/dl]	57.3 (13)	89.5 (17.2)	149.64 (26.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Super Tasters, Medium Tasters, Non Tasters
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.004
	Comments
	Method	ANOVA
	Comments

3. Secondary Outcome

Title	Association Between PROP Sensitivity and BMI
Description	Since individual ability to taste PROP may be correlated with BMI, we determined BMI (kg/m^2) in subjects classified as super-taster, medium taster and non-taster.Weight (kg) and height (m) were recorded for each subject.
Time Frame	7 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Super-tasters	Medium Tasters	Non-tasters
Arm/Group Description	Subjects highly sensitive to PROP	Subjects sensitive to PROP	Subjects no sensitive to PROP
Measure Participants	27	28	20
Mean (Standard Error) [Kg/m^2]	20.3 (0.48)	20.76 (0.58)	22.58 (0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Super Tasters, Medium Tasters, Non Tasters
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.048
	Comments
	Method	ANCOVA
	Comments	the three factors of the Stunkard and Messick Questionnaire were considered as covariates.

4. Secondary Outcome

Title	Electrophysiological Recordings From the Tongue for the Objective Evaluation of Individual Variations of 6-n-propylthiouracil (PROP) Sensitivity
Description	electrophysiological recordings from the tongue of 43 subjects classified for their taste sensitivity to 6-n- propyltiouracil (PROP) and genotyped for the specific receptor gene, TAS2R38. Density of fungiform papillae was also determined in each subject. The biopotentials were recorded by means of differential electrophysiological derivations between two silver electrodes, one in contact with the ventral surface of the tongue and one in perfect adhesion with the dorsal surface.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Relationship between depolarization amplitude of signals and PROP taster status.

Arm/Group Title	Super-Taster	Medium Taster	Non Taster
Arm/Group Description	Subjects highly sensitive to PROP	Subjects sentitive to PROP	Subjects no sensitive to PROP
Measure Participants	15	15	13
Mean (Standard Error) [mV]	97,08867 (6,538191)	75,42000 (6,538191)	48,48231 (7,023144)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Super Tasters, Medium Tasters, Non Tasters
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.00001
	Comments
	Method	ANOVA
	Comments

5. Secondary Outcome

Title	Association Between PROP Sensitivity and Fungiform Papilla Density
Description	43 subjects were classified for their taste sensitivity to 6-n- propyltiouracil (PROP) and density of fungiform papillae was determined in each subject.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Relationship between density of fungiform papillae and PROP taster status.

Arm/Group Title	Super-tasters	Medium Tasters	Non-tasters
Arm/Group Description	Subjects highly sensitive to PROP	Subjects sensitive to PROP	Subjects no sensitive to PROP
Measure Participants	15	15	13
Mean (Standard Error) [No./cm2]	51.66 (5.25)	33.49 (5.26)	18.53 (7.023)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Super Tasters, Medium Tasters, Non Tasters
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.00001
	Comments
	Method	ANOVA
	Comments

6. Secondary Outcome

Title	Taste Perception of Sweet, Sour, Salty, Bitter and Umami and Changes Due to L-Arginine Supplementation, as a Functin of Genetic Ability to Taste PROP.
Description	Taste perception was assessed by testing the ability to recognize, and the responsiveness to, representative solutions of the five taste qualities, also when supplemented with L-Arg, in subjects classified as PROP-tasters.
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Primary Taste Quality	Primary Taste Quality Supplemented With L-Arg
Arm/Group Description	we taste Sucrose, NaCl, Citric Acid, Caffeine and MSG	we taste Sucrose, NaCl, Citric Acid, Caffeine and MSG, each supplemented with L-Arginine (1:1)
Measure Participants	64	64
Undet Threshold	18 36%	2 2.9%
Correct identification	40 80%	20 28.6%
Incorrect teste response	6 12%	42 60%
Undet Threshold	1 2%	1 1.4%
Correct identification	52 104%	41 58.6%
Incorrect teste response	11 22%	22 31.4%
Undet Threshold	5 10%	4 5.7%
Correct identification	49 98%	47 67.1%
Incorrect teste response	10 20%	13 18.6%
Undet Threshold	6 12%	6 8.6%
Correct identification	56 112%	56 80%
Incorrect teste response	2 4%	2 2.9%
Undet Threshold	7 14%	0 0%
Correct identification	26 52%	33 47.1%
Incorrect teste response	31 62%	31 44.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Super Tasters, Medium Tasters
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.00001
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	7 months
Arm/Group Title	Super Tasters		Medium Tasters		Non Tasters
Arm/Group Description	Subjects highly sensitive to PROP		Subjects sensitive to PROP		Subjects no sensitive to PROP
All Cause Mortality
	Super Tasters		Medium Tasters		Non Tasters
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Super Tasters		Medium Tasters		Non Tasters
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/28 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Super Tasters		Medium Tasters		Non Tasters
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/28 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.