Department of Internal Medicine, Diabetology and Nephrology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland.
Department of Biochemistry and Medical Genetics, School of Health Sciences in Katowice, Medical University of Silesia, Medykow Street 18, 40-752 Katowice, Poland.
Nutrients. 2024 Sep 5;16(17):3002. doi: 10.3390/nu16173002.
Dairy products, a major source of calcium, demonstrate a number of beneficial effects, not only protecting against the development of osteoporosis (OP) but also suppressing the onset of type-2 diabetes (T2DM) and improving bone mineral density (BMD). Dairy consumption is closely linked to lactose tolerance. One of the genetic factors predisposing individuals to lactose intolerance is rs4988235 polymorphism of the MCM6 gene. The aim of this reported study was to analyse the relationship between the rs4988235 variant of the MCM6 gene and bone mineral density and the risk of type-2 diabetes in women after menopause.
The study was conducted among 607 female patients in the postmenopausal period in whom bone densitometry and vitamin-D3 levels were assayed and genotyping of the rs4988235 polymorphism of MCM6 gene was performed. The obtained results were analysed for the presence of T2DM, obesity surrogates, medical data, and past medical history.
The distribution of genotype frequencies was consistent with the Hardy-Weinberg equilibrium ( > 0.050). Postmenopausal women with the GG homozygote of rs4988235 polymorphism consumed significantly less calcium (dairy), which was probably related to the observed lactose intolerance. The GG homozygote of women with rs4988235 polymorphism was significantly more likely to have T2DM relative to the A allele carriers ( = 0.023). GG homozygotes had significantly lower femoral-vertebral mineral density despite the significantly more frequent supplementation with calcium preparations ( = 0.010), vitamin D ( = 0.01), and anti-osteoporotic drugs ( = 0.040). The obtained results indicate a stronger loss of femoral-neck mineral density with age in the GG homozygotes relative to the A allele carriers ( = 0.038).
In the population of women after menopause, the carriage of the G allele of rs4988235 polymorphism of the MCM6 gene, i.e., among the patients with lactose intolerance, significantly increased the risk of developing T2DM and the loss of BMD.
分析 MCM6 基因 rs4988235 变体与绝经后女性骨密度和 2 型糖尿病风险之间的关系。
本研究纳入了 607 名绝经后女性患者,对其进行骨密度和维生素 D3 水平检测,并对 MCM6 基因 rs4988235 多态性进行基因分型。分析了患者的 2 型糖尿病、肥胖替代指标、医疗数据和既往病史等结果。
基因型频率分布符合 Hardy-Weinberg 平衡(>0.050)。rs4988235 多态性 GG 纯合子的绝经后女性钙(乳制品)摄入量明显较少,这可能与观察到的乳糖不耐受有关。与 A 等位基因携带者相比,rs4988235 多态性女性的 GG 纯合子发生 2 型糖尿病的可能性显著更高(=0.023)。尽管 GG 纯合子更频繁地补充钙制剂(=0.010)、维生素 D(=0.01)和抗骨质疏松药物(=0.040),但股骨-脊柱骨矿物质密度明显较低。结果表明,与 A 等位基因携带者相比,GG 纯合子的股骨颈骨矿物质密度随年龄的增长下降得更快(=0.038)。
在绝经后女性人群中,MCM6 基因 rs4988235 多态性的 G 等位基因携带,即乳糖不耐受患者,显著增加了发生 2 型糖尿病和骨密度丧失的风险。