Mannan-binding protein (MBP) is a serum lectin participating in the innate immune defense by opsonizing various microorganisms for phagocytosis. Opsonization defect due to MBP deficiency and low levels of the protein can partially be explained by the dominant effect of three different mutations in the structural part of the MBP gene. Large interracial differences in the frequencies of these variants have previously been described, but they cannot explain the large interindividual variation in MBP serum concentration. We describe the existence of additional polymorphisms at positions -550 (H/L variants) and -221 (X/Y variants) in the promoter region of the gene. The promoter haplotypes, HY, LY, and LX, show associations with high, medium, and low levels of MBP serum concentrations, respectively. Moreover, this represents a genetic system with additive effect of haplotypes in which a low producing LX haplotype in the homozygous state down-regulates the basal expression of MBP as effectively as a single structural variant. Populations of pure Eskimos, Caucasoids, and black Africans show marked interethnic differences in the frequencies of promoter haplotypes regulating the expression of the normal peptide, with the HY haplotype frequency varying from 0.83 in Eskimos via 0.33 in Caucasoids to 0.08 in Africans. The LY haplotype frequency varies from 0.04 in Eskimos via 0.39 in Caucasoids to 0.23 in Africans. The LX haplotype frequency varies from 0.03 in Eskimos via 0.24 in Caucasoids to 0.23 in Africans. The effect of the promoter variants can explain almost all of the ethnic differences not explainable by the structural variants alone.

Context.—One of the controversies in preventive medicine is whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce the number of strokes and myocardial infarctions. In recent years the debate has been extended by studies indicating that reduced sodium intake has adverse effects.Objective.—To estimate the effects of reduced sodium intake on systolic and diastolic blood pressure (SBP and DBP), body weight, and plasma or serum levels of renin, aldosterone, catecholamines, cholesterols, and triglyceride, and to evaluate the stability of the blood pressure effect in relation to additional trials.Data Sources.—MEDLINE search from 1966 through December 1997 and reference lists of relevant articles.Study Selection.—Studies randomizing persons to high-sodium and low-sodium diets were included if they evaluated at least one of the effect parameters.Data Extraction.—Two authors independently recorded data.Data Synthesis.—In 58 trials of hypertensive persons, the effect of reduced sodium intake as measured by urinary sodium excretion (mean, 118 mmol/24 h) on SBP was 3.9 mm Hg (95% confidence interval [CI], 3.0-4.8 mm Hg) (P<.001) and on DBP was 1.9 mm Hg (95% CI, 1.3-2.5 mm Hg) (P<.001). In 56 trials of normotensive persons, the effect of reduced sodium intake (mean, 160 mmol/24 h) on SBP was 1.2 mm Hg (95% CI, 0.6-1.8 mm Hg) (P<.001) and on DBP was 0.26 mm Hg (95% CI, −0.3-0.9 mm Hg) (P=.12). The cumulative analysis showed that this effect size has been stable since 1985. In plasma, the renin level increased 3.6-fold (P<.001), and the aldosterone level increased 3.2-fold (P<.001); the increases were proportional to the degree of sodium reduction for both renin (r=0.66; P<.001) and aldosterone (r=0.64; P<.001). Body weight decreased significantly, and noradrenaline, cholesterol, and low-density lipoprotein cholesterol levels increased. There was no effect on adrenaline, triglyceride, and high-density lipoprotein cholesterol.Conclusion.—These results do not support a general recommendation to reduce sodium intake. Reduced sodium intake may be used as a supplementary treatment in hypertension. Further long-term studies of the effects of high reduction of sodium intake on blood pressure and metabolic variables may clarify the disagreements as to the role of reduced sodium intake, but ideally trials with hard end points such as morbidity and survival should end the controversy.

Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Accordingly, we investigated whether MBL variant alleles, which are associated with recurrent infections, might be risk factors for CF patients. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology, and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers of MBL variant alleles when compared with normal homozygotes. The negative impact of variant alleles on lung function was especially confined to patients with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infection was significantly more frequent in carriers of variant alleles than in homozygotes. The risk of end-stage CF among carriers of variant alleles increased 3-fold, and the survival time decreased over a 10-year follow-up period. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes. Presence of MBL variant alleles is therefore associated with poor prognosis and early death in patients with CF. J. Clin. Invest.104:431-437 (1999).