Polymorphism of the genetic determinants of bone mineral metabolism in various groups of the Komi people

The subject of the study is autochthonous population of the Northern and Middle Cis-Urals: Komi-Permyaks, Komi (Zyryans), and Komi-Izhems. The aim of the study is to compare the population frequencies of the LCT (rs4988235) and VDR (FokI rs2228570 and BsmI rs1544410) genes and to consider the contribution of environ-mental and cultural factors to the formation of differences in the genetic determinants of bone tissue metabolism. In total, 181 Komi-Permyak, 223 Komi, and 200 Komi-Izhem subjects were tested clinically and genetically. The evaluation consisted of the determination of polymorphic loci of VDR and LCT genes variants and assessment of clinical and laboratory lactase activity. The information on traditional diet and food composition was obtained from ethnographic materials. The study group of Komi-Izhems differs by a high proportion of C*LCT carriers (0.85) from the other two groups (p < 0.05). The prevalence of hypolactasia, i.e., limited lactase production, is also higher (p < 0.05) in Komi-Izhems (0.64) than in Komi-Permyaks (0.47) and Zyryans (0.41). The T*BsmI allele frequency is higher in Komi-Izems (0.493) in hetero- CT* (0.463) and homozygote TT* (0.261) genotypes, as compared to Zyryans (p < 0.05, where the frequencies are 0.377, 0.329 and 0.212, respectively). The values of BsmI allele and genotype frequencies in Komi-Permyaks are intermediate and do not differ significantly from those in Komi-Izhems and Zyryans. The concentration of T*FokI is highest in Komi-Permyaks (0.528). They are followed by Zyryans (the difference is insignificant, p > 0.05). Komi-Izhems have the smallest proportion of T*FokI allele carriers (0.400) and significantly differ from Komi-Permyaks (p = 0.01). The genotype distributions in FokI locus of VDR in the groups of Komi-Permyaks and Zyryans do not differ, but both show higher CT*FokI genotype frequencies than Komi-Izhems (0.549 and 0.569 against 0.288; p < 0.001). Poor livestock production and a lack of milk in the traditional subsistence economy of the Komi-Permyaks weakened the selection in favor of T*LCT allele and lactase persistence. The low intake of calcium with milk was compensated by an increase in the sensitivity of the target organs to calciferol, the regulator of mineral metabolism, by maintaining the high frequency of carriers of T*BsmI and T*FokI alleles of VDR gene in the population. The more productive dairy farming of Zyryans stimulated selection in favor of lactase persistence. The possibility of continuous consumption of calcium from milk eased the selection pressure on VDR loci. The regulation by T*FokI produced a physiologically sufficient effect and T*BsmI carriership remained low. The diet of the Komi-Izhems, who were accustomed to high-latitude regions, comprised low-lactose dairy products. The population preserved a high carriage of C*LCT and the phenotype of hypolactasia. Moderately intensive selection for vitamin D receptor sensitivity showed up in the increase of VDR T*BsmI frequency only. The high D-vitamin status of the Izhem people was leveraged by the traditional diet with a considerable intake of ergocalciferol-rich venison and fish. The Komi-Permyaks, Komi (Zyryans) and Komi-Izhems occupied different ecological niches and the groups found different ways to adapt to the unfavorable bone-homeorhesis conditions. The flexible responses to the pressure of the environmental factors were imple-mented by the selection of variants of LCT, VDR FokI and VDR BsmI genes, which are located in different chro-mosomes and determine different stages of mineral metabolism. We contend that modern interpopulation differences in distribution of the genotypes and alleles are the manifestations of different strategies of ecological adaptation of anthropologically related groups.

Dairy Consumption, Lactase Persistence, and Mortality Risk in a Cohort From Southern Sweden

Background: Whether high dairy consumption is related to longevity is still unclear, and additional studies of prospective cohorts with high-quality dietary data from populations with wide consumption ranges are needed.Objective: To examine the association between dairy consumption and mortality in a Swedish cohort.Design: Among 26,190 participants (62% females, 45–73 years old) without diabetes and cardiovascular disease from the population-based Malmö Diet and Cancer cohort, 7,156 individuals died during a mean follow-up time of 19 years. Data on intake of dairy (non-fermented milk, fermented milk, cheese, cream and butter) were collected from 7 day food records and food questionnaires. A genetic marker (rs4988235) associated with lactase persistence was detected among 22,234 individuals born in Sweden.Results: Higher intakes up to 1,000 g/day of non-fermented milk were associated with only marginal higher mortality rates after adjusting for potential confounders. However, intakes above 1,000 g/day (1.5% of the population) were associated with 34% (95% CI: 14, 59%, p-trend=0.002) higher mortality compared to that with &lt; 200 g/day. Fermented milk and cheese intake were inversely associated with mortality. Cream showed a protective association only among men. Butter was not associated with mortality. CT/TT genotype carriers (i.e., individuals with lactase persistence) had a 27% higher reported consumption of non-fermented milk, and non-significant higher mortality risk (HR = 1.08; 95% CI = 0.96, 1.23; p = 0.20) than CC genotype carriers.Conclusions: Higher mortality rates were mainly observed among participants consuming more than 1,000 g of non-fermented milk per day. In contrast, fermented milk and cheese were associated with lower mortality. Because dairy products differ in composition, it is important to examine them separately in their relation to health and disease. The use of a genetic variant as an objective marker of lactose-containing milk intake should be examined in relation to mortality in a larger population.

Tracing the Distribution of European Lactase Persistence Genotypes Along the Americas

In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the –13910∗T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase persistence phenotype, the –13910C &gt; T (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products. In the Americas, there is no evidence of the consumption of these products until the arrival of Europeans. However, several American countries’ dietary guidelines recommend consuming dairy for adequate human nutrition and health promotion. Considering the extensive use of dairy and the complex ancestry of Pan-American admixed populations, we studied the distribution of –13910C &gt; T lactase persistence genotypes and its flanking haplotypes of European origin in 7,428 individuals from several Pan-American admixed populations. We found that the –13910∗T allele frequency in Pan-American admixed populations is directly correlated with allele frequency of the European sources. Moreover, we did not observe any overrepresentation of European haplotypes in the –13910C &gt; T flanking region, suggesting no selective pressure after admixture in the Americas. Finally, considering the dominant effect of the –13910∗T allele, our results indicate that Pan-American admixed populations are likely to have higher frequency of lactose intolerance, suggesting that general dietary guidelines deserve further evaluation across the continent.

Development of a novel SNP assay to detect lactase persistence associated genetic variants

Background In adulthood the activity of the lactase enzyme is inherited as autosomal dominant form associated to Single nucleotide polymorphisms (SNPs). The present research was aimed to develop a novel genetic method to test lactase non persistence more powerfully. Methods and results In our study, we selected eight different SNPs that are associated with lactase persistence from Caucasian, Arabian Bedouins, sub-Saharian Africans and Asian populations to set up an approach to detect all the eight different SNPs at the same time in the same sample. This technique is centred on the identification of SNPs with a single nucleotide primer extension method using Sanger sequencing and capillary electrophoresis. Conclusions Our method allowed us to check the genotype asset of eight SNPs related to lactase persistence simultaneously and in a very efficient manner. It could be applied to a higher number of SNPs in a single reaction.

Evolution of Lactase Persistence: Turbo-Charging Adaptation in Growth Under the Selective Pressure of Maternal Mortality?

The emergence of the capacity to digest milk in some populations represents a landmark in human evolution, linking genetic change with a component of niche construction, namely dairying. Alleles promoting continued activity of the enzyme lactase through the life-course (lactase persistence) evolved in several global regions within the last 7,000 years. In some European regions, these alleles underwent rapid selection and must have profoundly affected fertility or mortality. Elsewhere, alleles spread more locally. However, the functional benefits underlying the rapid spread of lactase persistence remain unclear. Here, we set out the hypothesis that lactase persistence promoted skeletal growth, thereby offering a generic rapid solution to childbirth complications arising from exposure to ecological change, or to new environments through migration. Since reduced maternal growth and greater neonatal size both increase the risk of obstructed labour, any ecological exposure impacting these traits may increase maternal mortality risk. Over many generations, maternal skeletal dimensions could adapt to new ecological conditions through genetic change. However, this adaptive strategy would fail if ecological change was rapid, including through migration into new niches. We propose that the combination of consuming milk and lactase persistence could have reduced maternal mortality by promoting growth of the pelvis after weaning, while high calcium intake would reduce risk of pelvic deformities. Our conceptual framework provides locally relevant hypotheses to explain selection for lactase persistence in different global regions. For any given diet and individual genotype, the combination of lactase persistence and milk consumption would divert more energy to skeletal growth, either increasing pelvic dimensions or buffering them from worsening ecological conditions. The emergence of lactase persistence among dairying populations could have helped early European farmers adapt rapidly to northern latitudes, East African pastoralists adapt to sudden climate shifts to drier environments, and Near Eastern populations counteract secular declines in height associated with early agriculture. In each case, we assume that lactase persistence accelerated the timescale over which maternal skeletal dimensions could change, thus promoting both maternal and offspring survival. Where lactase persistence did not emerge, birth weight was constrained at lower levels, and this contributes to contemporary variability in diabetes risk.

Relation of the C/T-13910 LCT Polymorphism with Body Composition Measures and Their Modulation by Dairy Products in a Caucasian Men

The C/T-13910 LCT is closely associated with lactase persistence and LCT has emerged as a new candidate gene for obesity, in particular in northern Europeans. The aim of this research is to investigate to what degree sex determines the association between the LCT variant and anthropometric traits in a cohort of healthy individuals. We recruited 1000 (500 males and 500 females aged 18–65 years) healthy blood donors. The C/T-13910 LCT polymorphism was genotyped using TaqMan assays. All individuals were phenotyped with respect to anthropometric characteristics. Prevalence of genotypes was 22.7% CC (lactase non-persistent, LNP), 58.6% CT, and 18.7% TT. LNP genotype was present less frequently among men p = .0005; OR 0.582 [0.425–0.794]. Therefore, in addition statistical calculations were performed separately for men and women. Additional analysis demonstrated an association between the CC genotypes and higher chest ( p = .03), waist ( p = .005), and forearm circumference ( p = .0004) or more lean body mass ( p = .04), than T-allele carriers in males. In females, they were not significantly different. Men consumed more milk ( p = .003), while women ate more yoghurt ( p = .001). Pearson’s correlation analysis showed that the higher intake of milk and dairy products was associated with higher fat body mass among men with lactase persistence. In Caucasian men, the LNP genotype is associated with reduced milk intake and dairy products, but more fat-free mass and higher forearm circumference, which may be relevant to dietary management for lactose intolerant.