Adult-type hypolactasia is not a predisposing factor for the early functional and structural changes of atherosclerosis: the Cardiovascular Risk in Young Finns Study

Abstract

Individuals suffering from ATH (adult-type hypolactasia), defined by the LCT (gene encoding lactase-phlorizin hydrolase) C/C(-13910) genotype (rs4988235), use less milk and dairy products and may have higher plasma HDL (high-density lipoprotein) and lower triacylglycerol (triglyceride) concentrations than their counterparts without ATH. To investigate the effects of ATH status on the early markers of atherosclerosis, we examined its association with CIMT (carotid intima-media thickness), CAC (carotid artery compliance) and brachial artery FMD (flow-mediated dilation) in a young population-based cohort of otherwise healthy individuals. As part of the Cardiovascular Risk in Young Finns Study, we performed CIMT, CAC and FMD analyses, LCT C/T(-13910) genotyping and risk factor determination in 2109 young subjects 24-39 years of age (45% males) at the time of the examination. The consumption of both milk and dairy products was lowest and the consumption of alcohol highest in subjects with the C/C(-13910) genotype (P<0.001 for all) in comparison with subjects without ATH (TT+CT). In multivariate analysis, no significant association between ATH status and CIMT, CAC or brachial artery FMD was found after adjustment for the use of alcohol, dairy products and all other major risk factors of coronary artery disease. In otherwise similar statistical analysis, the results remained non-significant when females and males were analysed in their own groups. In conclusion, the finding does not support the involvement of ATH in the pathogenesis of early atherosclerosis.

Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis

“…The gastrointestinal symptoms in response to lactose that occur (at varying levels) in individuals with adult-type hypolactasia motivated investigation of the positive association between LP and intake of milk and other dairy products 2 , 11 , 12 . This association was observed in several populations 13–18 but not universally, possibly for cultural reasons involved with acceptance and generality of milk drinking 19 , 20 …”

“…For some studies 13 , 16 , 19 , 30 , 43–52 it was necessary to calculate the standard error of the mean difference (SE). This was performed as follows: $\text{SE\hspace{0.17em}=\hspace{0.17em}}\sqrt{{\text{s}}_{\text{CC}}^{\text{2}}{\text{/n}}_{\text{CC}}{\text{+s}}_{\text{LP}}^{\text{2}}{\text{/n}}_{\text{LP}}}\text{,}$ where and s i and n i are the standard deviation and sample size, respectively, for non-LP (i = CC) and LP (i = LP) individuals.…”

“…non-persistents) 36 . Given that genetically-defined LP has been associated with higher milk intake in these populations, 13–18 the association between LP and BMI may be due to differences in milk consumption. However, the aforementioned large Danish study did not detect strong associations with obesity and blood pressure 30 , 37 …”

Frequency of lactase persistence genotype in a healthy Polish population

“…A single nucleotide polymorphism (SNP) C/T (located -13910 bp upstream from the start codon of the LPH, within intron 13 of MCM6 (minichromosome maintenance complex component 6), is strongly associated with lactase non-persistence/persistence in Europeans [10]. The homozygous LCT-13910 C variant (the C/C genotype) is associated with hypolactasia, while the LCT-13910 T allele (C/T and T/T genotypes) is responsible for lactase persistence [11]. The transcriptional activation of the lactase promoter and the level of lactase protein production depends on the T/C variant, thus the SNP operates as cis regulatory element of the lactase gene [12].…”

Dairy Consumption, Plasma Lipoproteins, and Cardiovascular Risk: Finding the Balance

“…Individuals homozygous for the C allele (LNP) have almost undetectable levels of intestinal lactase production compared to TC or TT individuals (lactase persistent ([LP]). Variations in the lactase gene have mainly been studied in relation to the quantity of milk and dairy products consumed [55], and several studies have found that individuals with the LNP genotype consume less milk [52,53,55], although this association has not always been found [54•]. Some studies have reported an association between the LP genotype and higher body mass index [56] and risk of metabolic syndrome [53].…”