Investigating the HLA component in rheumatoid arthritis: an additive (dominant) mode of inheritance is rejected, a recessive mode is preferred.

We examined the mode of inheritance of rheumatoid arthritis (RA) and estimated the genetic contribution of the HLA-linked locus to the development of RA using data from 111 multiplex families (54 London, 57 Cleveland), and 43 randomly ascertained patients (Seattle). HLA-DR4 was present in 78 multiplex probands (70%); a further 16 probands who were negative for DR4 were positive for DR1. Both DR4 and DR1 were significantly in excess when compared to control population frequencies (P less than 0.001); an additional finding was an excess of DR7, although the numbers of probands with DR7 were small. Despite the well-established HLA association with RA, neither recessive nor additive (dominant) modes of inheritance, nor any intermediate models have been ruled out using affected sib-pair and antigen genotype frequency among patients (AGFAP) methods. However, in our study the AGFAP data for HLA-DR4 and DR1 were close to recessive expectations (P = ns) while an additive (dominant) mode of inheritance was rejected (P less than 0.001). The same results were obtained by an independent method which considered HLA-DR transmission from affected parents to their affected children. The affected sib-pair haplotype sharing method showed deviation from random expectations but did not allow discrimination between recessive and additive (dominant) modes. The effect of the HLA-linked locus on familiarity accounted for only a 1.61-fold increased risk to sibs over the population prevalence, compared to an observed value of 3.90. This indicated that there could be at least one other non-HLA locus predisposing to RA with a weight that is slightly greater than that of HLA.     

Epistatic modeling in rheumatoid arthritis: An application of the Risch theory

Rheumatoid arthritis (RA) is a disease of unknown etiology but with a presumed complex pattern of inheritance. Risch [Am J Hum Genet 46:222–228, 1990] has shown that the recurrence risk ratio, λ_R, (which is defined as the risk to type R relatives vs. the population prevalence) can be used to evaluate patterns of inheritance in genetically complex diseases. We have used the Risch theory to examine some multiple locus models of inheritance in RA. Recurrence risk ratios in MZ twins and in 1st, 2nd, and 3rd degree relatives are summarized from the literature. The limited data available supports at least a two-locus model of inheritance for RA (assuming that one locus is HLA). Better estimates of the recurrence risk ratios in RA families are required so that the Risch theory can be pursued further. © 1993 Wiley-Liss, Inc.     

Power of the linkage test for a heterogeneous disorder due to two independent inherited causes: a simulation study

We have conducted a simulation study in small pedigrees to investigate the power to detect linkage and heterogeneity for a disorder due to either one of two independent disease loci. We have considered a highly polymorphic marker locus (PIC = 70%) linked to one disease locus and unlinked to the second. The power to detect linkage has been examined by using the admixture test. We have varied the mode of transmission of each disease locus, the ascertainment of families and the proportion of cases in the population due to the linked disease locus. Generally, for the multiplex ascertainments we have considered, the power to detect linkage is greater when the linked disease locus has a high penetrance, when the unlinked disease locus has a low penetrance, and when pedigrees with multiple affected are selected. When selecting families with multiple affected, the rate of "mixed" families (i.e., those segregating for both disease loci) increases. However, for the pedigree structure we have considered, the power of the linkage test is more affected by a decrease in the rate of "linked" families than by an increase in the rate of "mixed" families. Finally, the present study shows that detection of linkage in presence of heterogeneity is feasible with a realistic sample size of small pedigrees as long as the linked disease locus accounts for more than 25% of the cases.     

新型服务模式下深圳市福田区不同年龄新婚人群的婚检意愿调查及干预对策

目的 探讨新型服务模式下不同年龄新婚人群的婚前检查意愿调查。 方法 选取2015年9月-2016年4月1 600例新婚人群为研究对象,按照年龄,将其均分为≤25岁、>25~30岁、>30~35岁、>35岁四组,采用自制调查问卷调查并分析新婚人群不同年龄组婚前检查意愿,提出针对性的干预对策。 结果 不同年龄组婚检调查问卷得分分布差异有统计学意义(χ²=76.190,P=0.000),>35岁新婚人群的婚检认知较≤25岁、>25~30岁、>30~35岁低(χ²₁=53.517、χ²₂=31.631、χ²₃=24.555,P<0.007);不同年龄组婚前体检必要性认知情况分布差异有统计学意义(χ²=39.702,P=0.000),>35岁新婚人群认为婚检有必要的相对较≤25岁、>25~30岁、>30~35岁低(χ²₁=31.634、χ²₂=22.893、χ²₃=14.875,P<0.007);81.38%(1 302例)愿意参与免费婚检,18.63%(298例)不愿意参与免费婚检。不同年龄组参加免费婚检意愿率差异有统计学意义(χ²=38.285,P=0.000),其中,≤25岁愿意参加免费婚检率较>30~35岁及>35岁高(χ²₁=15.885、χ²₂=17.852,P<0.05),>25~30岁愿意参加免费婚检率较>30~35岁及>35岁高(χ²₁=20.224、χ²₂=22.418,P<0.007);愿意便于了解男女双方的健康状况、及时发现疾病、预防子代出生缺陷是愿意参与婚检的主要原因。觉得不重要、在单位常规体检过是不愿意参与婚检的主要原因;二分类logistic回归分析,结果发现:学历高(OR=0.056)、婚检重要性(OR=0.039)及必要性(OR=0.055)认识充分是愿意参加免费婚检的保护因素。害怕查出有病对方不结婚(OR=7.076)是愿意参加免费婚检的危险因素。 结论 新型服务模式下,年龄较低的新婚人群婚检意愿较高,新婚人群对于婚检认识还有待加强,规范婚检服务,加强宣传教育工作,促进婚检重要性及必要性认识,仍是今后工作的重点。     

紧密型医联体“院地”服务模式实践与成效——以四川大学华西医院为例

目的 探寻跨组织医疗服务的“院地”服务模式的实践特点和其关键成功因素,为紧密型医联体建设与发展提供依据。方法 跟踪调查华西医院与成都市成华区政府开展的“院地”紧密型医联体建设过程和方法,对华西-成华医联体 “N+1+N”联盟架构中转诊绿色通道、检验同质化、家庭医生团队、信息化支撑的多项服务进行分析评价。结果 紧密型医联体的成效集中在基层医疗、上下联动、患者满意度、双向转诊制度等多个方面。结论 紧密型医联体服务模式成效显著,能充分适应“大健康”战略要求,为深化医联体服务创新能力、发挥更深层次效用打下坚实基础。