A global multicenter study on reference values: 2. Exploration of sources of variation across the countries.
OBJECTIVE
The intent of this study, based on a global multicenter study of reference values (RVs) for serum analytes was to explore biological sources of variation (SVs) of the RVs among 12 countries around the world.


METHODS
As described in the first part of this paper, RVs of 50 major serum analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry. Multiple regression analysis was performed for each gender, country by country, analyte by analyte, by setting four major SVs (age, BMI, and levels of drinking and smoking) as a fixed set of explanatory variables. For analytes with skewed distributions, log-transformation was applied. The association of each source of variation with RVs was expressed as the partial correlation coefficient (rp).


RESULTS
Obvious gender and age-related changes in the RVs were observed in many analytes, almost consistently between countries. Compilation of age-related variations of RVs after adjusting for between-country differences revealed peculiar patterns specific to each analyte. Judged fromthe rp, BMI related changes were observed for many nutritional and inflammatory markers in almost all countries. However, the slope of linear regression of BMI vs. RV differed greatly among countries for some analytes. Alcohol and smoking-related changes were observed less conspicuously in a limited number of analytes.


CONCLUSIONS
The features of sex, age, alcohol, and smoking-related changes in RVs of the analytes were largely comparable worldwide. The finding of differences in BMI-related changes among countries in some analytes is quite relevant to understanding ethnic differences in susceptibility to nutritionally related diseases.
Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: ichihara@yamaguchi-u.ac.jp.
Kiyoshi
K
Ichihara
Department of Medical Biochemistry, Uludag University School of Medicine, Bursa, Turkey.
Yesim
Y
Ozarda
Blood Sciences, Leeds General Infirmary, Leeds, UK.
Julian H
JH
Barth
Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.
George
G
Klee
Department of Medical Life Science, Faculty of Medical Bioscience, Kyushu University of Health and Welfare, Nobeoka, Japan.
Yoshihisa
Y
Shimizu
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.
Liangyu
L
Xia
Division of Chemical Pathology, University of Stellenbosch, National Health Laboratory Services, Tygerberg, South Africa.
Mariza
M
Hoffmann
Department of Laboratory Medicine, P. D. Hinduja National Hospital and Medical Research Center, Mumbai, India.
Swarup
S
Shah
Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town, South Africa.
Tandi
T
Matsha
PathCare Laboratories, Cape Town, South Africa.
Janette
J
Wassung
Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, Cape Town, South Africa; PathCare Laboratories, Cape Town, South Africa.
Francois
F
Smit
Beckman Coulter LLC, Moscow, Russia.
Anna
A
Ruzhanskaya
ARUP Laboratories, University of Utah School of Medicine, Salt Lake City, UT, USA.
Joely
J
Straseski
Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Daniel N
DN
Bustos
Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Shogo
S
Kimura
Beckman Coulter Japan, Tokyo, Japan.
Aki
A
Takahashi
D000367:Age Factors; D015992:Body Mass Index; D019411:Clinical Laboratory Techniques / Q000592:standards*; D005006:Ethnicity; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D012016:Reference Values; D012737:Sex Factors
Age-related changes; Alcohol-related changes; BMI-related changes; Body mass index (BMI); Ethnicity-related changes; Multiple regression analysis; Reference values; Smoking-related changes; Worldwide multicenter study