Low Childhood Cholesterol Absorption Predisposes to Gallstone Disease: The Cardiovascular Risk in Young Finns Study.
Unraveling pathogenesis of gallstones could help to diminish its enormous disease burden. We hypothesized that certain properties of childhood cholesterol metabolism predict gallstone disease in adulthood.



Childhood serum cholestanol and plant sterols (surrogates for cholesterol absorption), cholesterol precursors (surrogates for cholesterol synthesis), lipids, demographics, and dietary habits were compared between individuals diagnosed with gallstone disease subsequently in adulthood (n = 95) and control subjects (n = 190) matched for age, sex, and body mass index in 1980. Subjects were participants of prospective Cardiovascular Risk in Young Finns Study.



In 1980, at mean age of 11.4 years gallstone cohort was characterized by 5.8% lower cholestanol (P = 0.038), and 11.2% to 12.2% (P range = 0.003-0.008) lower plant sterols campesterol, sitosterol, and avenasterol compared with controls. Mean lathosterol/sitosterol ratio was 16.3% higher in gallstone compared with control cohort (P = 0.028). Female gallstone group had 5.4% lower mean cholestanol compared with controls (P < 0.05), and, respectively, those of campesterol, sitosterol, and avenasterol were 12.7% to 14.0% lower (P < 0.05 for each). Body mass index was inversely related to cholestanol and sitosterol (r range = -0.161 to -0.208, P < 0.05 for each) in controls, but not among patients with gallstone. In whole study population, surrogates of cholesterol absorption (eg, campesterol, P = 0.018) and low dietary intake of vegetables (P = 0.009) were significant predictors of gallstones in logistic regression model.



Cholesterol metabolism trait characterized by low serum levels of surrogate markers of cholesterol absorption precedes adult gallstone disease already in childhood. Low serum cholestanol and plant sterol ratios during normal Western diet may have role as predictive biomarkers for gallstones.
*Clinic of Gastroenterology, Abdominal Center †Clinic of Cardiology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki ‡Department of Medicine, University of Turku §Division of Medicine, Turku University Hospital, Turku ||Department of Pediatrics, Tampere University Hospital and University of Tampere, Tampere ¶Hospital for Children and Adolescents, University of Helsinki, Helsinki #Oulu University Hospital, PEDEGO Research Group and Medical Research Center, University of Oulu, Oulu **Department of Clinical Physiology, University of Eastern Finland and Kuopio University Hospital, Kuopio ††The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku ‡‡Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku §§Pediatric Surgery, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Markku J
MJ
Nissinen
Piia
P
Simonen
Helena
H
Gylling
Jorma
J
Viikari
Nina
N
Hutri-Kähönen
Eero
E
Jokinen
Päivi
P
Tossavainen
Tomi
T
Laitinen
Olli
O
Raitakari
Markus
M
Juonala
Mikko P
MP
Pakarinen
D065567:Absorption, Physiological; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood*; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D042882:Gallstones / Q000175:diagnosis / Q000209:etiology*; D006306:Health Surveys; D006801:Humans; D008297:Male; D010840:Phytosterols / Q000097:blood; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
D015415:Biomarkers; D010840:Phytosterols; D002784:Cholesterol